Prostate specific membrane antigen (PSMA) ligands and uses thereof

Abstract

The present application relates to compounds of formula (I). # imgabs0 #

Description

Technical Field

[0001] The present invention relates to a compound; a ligand for prostate-specific membrane antigen (PSMA); a composition comprising the compound; the compound or the composition, respectively, for use in a method for diagnosing a disease; the compound or the composition, respectively, for use in a method for treating a disease; the compound or the composition, respectively, for use in a method for diagnosing and treating a disease (also known as "thera(g)nosis" or "thera(g)nostics"); the compound or the composition, respectively, for use in a method for delivering a therapeutically active nuclide or a diagnostically active nuclide to a tissue expressing PSMA; a method for diagnosing a disease using the compound or the composition, respectively; a method for treating a disease using the compound or the composition, respectively; a method for diagnosing and treating a disease using the compound or the composition, respectively (also known as "thera(g)nosis" or "thera(g)nostics"); a method for delivering a therapeutically active nuclide or a diagnostically active nuclide to a tissue expressing PSMA using the compound or the composition, respectively. Background Art

[0002] Prostate cancer (PCa) is one of the most common cancers in men and the second most common cause of cancer-related death in men after lung cancer. The risk of developing prostate cancer increases dramatically with age, especially in men over 50 years old. With the aging population and increased life expectancy over the past three decades, the incidence of prostate cancer in the United States has approached one in six men.

[0003] Early diagnosis and successful treatment of prostate cancer remain a major clinical challenge. In addition to new technologies for the accurate detection of prostate lesions, understanding the major molecular cascades involved in prostate carcinogenesis, metastasis, and drug resistance is crucial for the development of new therapeutic agents and intervention strategies. A molecular hallmark of prostate cancer is the aberrant expression of the transmembrane glycoprotein prostate-specific membrane antigen (PSMA) on the plasma membrane of virtually all prostate tumors. The expression profile of PSMA in prostate cancer and its limited expression in normal organs suggest that it may play an important role in prostate cancer and represents an attractive target for pharmacological intervention. The ability to target PSMA for the specific delivery of anticancer compounds may aid in the treatment of PSMA-expressing cancers as well as other diseases and conditions.

[0004] PSMA is a transmembrane, 750 amino acid, type II glycoprotein (SEQ ID NO: 1) that is abundantly and restrictedly expressed on the surface of prostate cancer, particularly in androgen-independent, advanced, and metastatic disease. The latter is important because almost all prostate cancers become androgen-independent over time. PSMA has the criteria of a promising therapeutic target, namely, abundant and restricted expression (restricted to the prostate) at all stages of the disease, presence on the cell surface but not shed into the circulation, and association with enzymatic or signaling activity. Under androgen deprivation therapy, metastatic spread and disease progression mark the development of metastatic castration-resistant prostate cancer (mCRPC), a fatal form of the disease that severely reduces the patient's quality of life. Although therapies have been approved for the treatment of mCRPC, their survival benefit is generally limited to less than 6 months.

[0005] PSMA is also present in the endothelial cells of neovascularization in non-prostate tumors, including those of the kidney, lung, stomach, colon, and breast, where it promotes endothelial cell proliferation and invasion by regulating proteases that cleave the extracellular matrix.

[0006] Selectively targeting cancer cells with radiopharmaceuticals, whether for imaging or therapeutic purposes, is a challenge. A variety of radionuclides are known for use in radioimaging or cancer radiotherapy.

[0007] Despite significant advances in the diagnosis and treatment of cancer, improved treatments are still sought. There is a clinical need for improved treatments for cancer, such as prostate cancer, including treatments that can provide more effective and / or longer-lasting responses. Summary of the Invention

[0008] One aspect of the present application relates to compounds of formula (I)

[0009]

[0010] in

[0011] X is selected from a bond and -CH2-;

[0012] Z 1 Selected from chelating agents and NT;

[0013] NT is selected from the group consisting of H, Ac, Hex, HPA, HO-succinyl, SaPr, Iva, HYDAc, Bio, nBuCAyl, AF488Ahx, and Hib;

[0014] L 1 Selected from a bond and -(Xaa1) k -,

[0015] k is selected from 1, 2 and 3,

[0016] Xaa1 is each independently an amino acid residue, preferably, the amino acid residue is selected from α-amino acid residue, β-amino acid residue, γ-amino acid residue, δ-amino acid residue, ε-amino acid residue, ω-amino acid residue and an amino acid residue of formula (YI),

[0017]

[0018] g is an integer selected from 0-23,

[0019] in,

[0020] If k=1, then Xaa1 and Z 1 covalently bound to and covalently bound to Xaa2,

[0021] If k=2, then the first of the two Xaa1 and Z 1 covalently bound to and covalently bound to the second of the two Xaa1s, and the second of the two Xaa1s is covalently bound to the first of the two Xaa1s and covalently bound to Xaa2,

[0022] If k=3, then the first of the three Xaa1 and Z 1 covalently bound to and covalently bound to the second of the three Xaa1s, the second of the three Xaa1s is covalently bound to the first of the three Xaa1s and covalently bound to the third of the three Xaa1s, and the third of the three Xaa1s is covalently bound to the second of the three Xaa1s and covalently bound to Xaa2;

[0023] When L 1 When Z is a key, 1 is NT;

[0024] Xaa2 is selected from formula (II) and formula (III):

[0025]

[0026] where R 2a Selected from H, (C1-C6) alkyl and CH2R 2g ;

[0027] R 2g Selected from OH and CO2H;

[0028] R 2b selected from H and (C1-C6)alkyl;

[0029] Or, R 2a and R 2bcan form a 5- or 6-membered carbocyclic or heterocyclic ring together,

[0030] R 2c selected from H and CH3;

[0031] R 2d selected from H, F and OH;

[0032] R 2e Selected from H and F;

[0033] R 2f selected from H and CH3;

[0034] The condition is that when L 1 Xaa2 may not be present when it is a bond and NT is Hib;

[0035] Xaa3 is selected from formula (IV):

[0036]

[0037] where R 3a is selected from aryl, (C5-C6)heteroaryl, indol-3-yl, 6-chloro-1H-indol-3-yl and -S-CH2-phenyl; and wherein R 3a The aryl or heteroaryl ring is optionally substituted with 1, 2 or 3 substituents independently selected from halogen, (C1-C6)alkyl, CN, OH, -O(C1-C3)alkyl, wherein the (C1-C6)alkyl may be optionally substituted with one or more fluorine;

[0038] R 3b selected from H and CH3;

[0039] h is selected from 1 and 2;

[0040] Xaa5 is selected from the group consisting of Formula (Va), Formula (Vb), Hgn, Lys, Nle, Tap, Aph, and Gln:

[0041]

[0042] where R 5a Selected from H, (C1-C6) alkyl, Ac, C(=NR 5d )NR 5e R 5f and Bio;

[0043] R 5d selected from H and CH3;

[0044] R 5e and R 5f independently selected from H and (C1-C6)alkyl;

[0045] R5b selected from H and (C1-C6)alkyl;

[0046] R 5c Selected from H and CH3;

[0047] m is selected from 2, 3, 4 and 5; and

[0048] R 5g 、R 5h and R 5i independently selected from (C1-C6)alkyl;

[0049] Xaa6 is selected from Formula (VI), Formula (VII), Nle and arg:

[0050]

[0051] where R 6a Selected from H, C(=NR 6e )NR 6f R 6g 、C(=O)R 6h and pyridyl;

[0052] R 6e selected from H and CH3;

[0053] R 6f Selected from H, (C1-C6) alkyl, Ac, NO2 and C(=O)NR 6i R 6j ;

[0054] R 6i and R 6j independently selected from H and (C1-C2)alkyl;

[0055] R 6g selected from H and (C1-C6)alkyl;

[0056] Or, R 6e and R 6f They can form a 5- or 6-membered heterocyclic ring.

[0057] R 6h Selected from (C1-C6) alkyl, NR 6k R 6m and NR 6n C(=NR 6p )NR 6q R 6r ;

[0058] R 6k and R 6m independently selected from H and (C1-C6)alkyl;

[0059] R6n and R 6p independently selected from H and CH3;

[0060] R 6q and R 6r independently selected from H and (C1-C6)alkyl;

[0061] R 6b selected from H and (C1-C6)alkyl;

[0062] R 6c selected from H and CH3;

[0063] n is selected from 1, 2, 3 and 4;

[0064] R 6d Selected from NR 6s C(=NR 6t )NR 6u R 6v , OH and NR 6w R 6x ;

[0065] R 6s and R 6t independently selected from H and CH3;

[0066] R 6u 、R 6v 、R 6w and R 6x independently selected from H and (C1-C6)alkyl; and

[0067] q is selected from 2, 3 and 4;

[0068] Xaa7 is an amino acid residue, wherein the amino acid residue is preferably selected from Formula (VIII), Formula (IX), Formula (X), Formula (XI), Dtc and Oic:

[0069]

[0070] where R 7a Selected from H, (C1-C6) alkyl and (CH2) t R 7g ;

[0071] R 7g Selected from OH, CO2H and NR 7h R 7i ;

[0072] R 7h and R 7i independently selected from H and (C1-C6)alkyl;

[0073] t is selected from 1, 2, 3 and 4;

[0074] R 7b selected from H and (C1-C6)alkyl;

[0075] Or, R 7a and R 7b can form a 5- or 6-membered carbocyclic or heterocyclic ring together,

[0076] R 7c selected from H and CH3;

[0077] R 7d selected from H, F and OH;

[0078] R 7e Selected from H and F;

[0079] R 7f selected from H and CH3;

[0080] u is selected from 2, 3 and 4;

[0081] L 3 Selected from bonds and -(Xab1) v -;

[0082] Wherein v is selected from 1, 2 and 3,

[0083] Xab1 is each independently an amino acid residue, preferably, the amino acid residue is selected from α-amino acid residue, β-amino acid residue, γ-amino acid residue, δ-amino acid residue, ε-amino acid residue, ω-amino acid residue and an amino acid residue of formula (YI),

[0084] If v=1, then Xab1 and Z 3 covalently bound to the side chain amino functional group of formula (X) or formula (XI),

[0085] If v=2, the first of the two Xab1 and Z 3 covalently bound to the second of the two Xab1, and the second of the two Xab1 is covalently bound to the first of the two Xab1 and covalently bound to the side chain amino functional group of formula (X) or formula (XI),

[0086] If v=3, the first of the three Xab1 and Z 3 covalently bound to the second of the three Xab1s and covalently bound to the third of the three Xab1s, and the third of the three Xab1s is covalently bound to the second of the three Xab1s and covalently bound to the side chain amino functional group of formula (X) or formula (XI);

[0087] Z 3 Selected from H and a chelating agent;

[0088] Xaa8 is an α-amino acid residue, wherein the α-nitrogen atom of Xaa8 is unsubstituted or optionally substituted with CH3;

[0089] Xaa10 is formula (XII):

[0090]

[0091] in:

[0092] R 10a Selected from (C1-C6)alkyl;

[0093] R 10b selected from H and (C1-C6)alkyl;

[0094] Or, R 10a and R 10b can form a 5- or 6-membered carbocyclic or heterocyclic ring together,

[0095] R 10c selected from H and CH3;

[0096] L 2 Selected from: bond and -Xaa11-(Xaa12) s -, so that Xaa11 and Xaa10 are covalently bound;

[0097] Xaa11 is an amino acid residue, wherein the amino acid residue is preferably selected from the group consisting of an α-amino acid residue, a β-amino acid residue, a γ-amino acid residue, a δ-amino acid residue, an ε-amino acid residue, an ω-amino acid residue and an amino acid residue of formula (YI);

[0098] s is selected from the group consisting of 0, 1, 2, 3, 4, and 5; and

[0099] Xaa12 are each independently an amino acid residue, wherein the amino acid residue is preferably selected from the group consisting of an α-amino acid residue, a β-amino acid residue, a γ-amino acid residue, a δ-amino acid residue, an ε-amino acid residue, an ω-amino acid residue and an amino acid residue of formula (YI),

[0100] If s=0, then Xaa11 and Z 2 covalently bound,

[0101] If s=1, Xaa12 is covalently bound to Xaa11 and to Z 2 covalently bound,

[0102] If s=2, the first of the two Xaa12 is covalently bound to Xaa11 and covalently bound to the second of the two Xaa12, and the second of the two Xaa12 is covalently bound to the first of the two Xaa12 and covalently bound to Z 2 covalently bound,

[0103] If s=3, the first of the three Xaa12 is covalently bound to Xaa11 and covalently bound to the second of the three Xaa12, the second of the three Xaa12 is covalently bound to the first of the three Xaa12 and covalently bound to the third of the three Xaa12, and the third of the three Xaa12 is covalently bound to the second of the three Xaa12 and covalently bound to Z. 2 covalently bound,

[0104] If s=4, the first of the four Xaa12 is covalently bound to Xaa11 and covalently bound to the second of the four Xaa12, the second of the four Xaa12 is covalently bound to the first of the four Xaa12 and covalently bound to the third of the four Xaa12, the third of the four Xaa12 is covalently bound to the second of the four Xaa12 and covalently bound to the fourth of the four Xaa12, and the fourth of the four Xaa12 is covalently bound to the third of the four Xaa12 and covalently bound to Z. 2 covalently bound,

[0105] If s=5, the first of the five Xaa12 is covalently bound to Xaa11 and covalently bound to the second of the five Xaa12, the second of the five Xaa12 is covalently bound to the first of the five Xaa12 and covalently bound to the third of the five Xaa12, the third of the five Xaa12 is covalently bound to the second of the five Xaa12 and covalently bound to the fourth of the five Xaa12, the fourth of the five Xaa12 is covalently bound to the third of the five Xaa12 and covalently bound to the fifth of the five Xaa12, and the fifth of the five Xaa12 is covalently bound to the fourth of the five Xaa12 and covalently bound to Z 2 covalent binding;

[0106] Z 2 An α-amino acid residue selected from CT, XDa-chelating agents and formula (CT-I):

[0107]

[0108] CT is selected from the group consisting of formula (CT-II), formula (CT-III), AF488N3K-NH2, OH, and Throl-OH:

[0109]

[0110] in:

[0111] R CT1 selected from H and CH3;

[0112] R CT2 selected from H and (C1-C6)alkyl;

[0113] R CT3 and R CT4 are each independently selected from H and CH3;

[0114] R CT5 selected from H and (C1-C6)alkyl;

[0115] x is selected from 2 to 10;

[0116] XDa is a diamine, wherein the diamine is preferably selected from en and Ape;

[0117] w is selected from 1, 2, 3, 4, 5 and 6;

[0118] L 4 Selected from bonds and -(Xac1) y -,

[0119] in:

[0120] y is selected from 0, 1, 2 and 3,

[0121] Xac1 is each independently an amino acid residue, preferably, the amino acid residue is selected from α-amino acid residue, β-amino acid residue, γ-amino acid residue, δ-amino acid residue, ε-amino acid residue, ω-amino acid residue and an amino acid residue of formula (YI),

[0122] If y=0, the side chain amino functional group of the α-amino acid residue of formula (CT-I) is 4 covalently bound,

[0123] If y=1, Xac1 is covalently bound to the side chain amino functional group of the α-amino acid residue of formula (CT-I) and to Z 4 covalently bound,

[0124] If y=2, the first of the two Xac1 is covalently bound to the side chain amino functional group of the α-amino acid residue of formula (CT-I) and covalently bound to the second of the two Xac1, and the second of the two Xac1 is covalently bound to the first of the two Xac1 and to Z 4 covalently bound,

[0125] If y=3, the first of the three Xac1 is covalently bound to the side chain amino functional group of the α-amino acid residue of formula (CT-I) and covalently bound to the second of the three Xac1, the second of the three Xac1 is covalently bound to the first of the three Xac1 and covalently bound to the third of the three Xac1, and the third of the three Xac1 is covalently bound to the second of the three Xac1 and covalently bound to Z 4 covalently bound,

[0126] If y=4, the first of the four Xac1 is covalently bound to the side chain amino functional group of the α-amino acid residue of formula (CT-I) and covalently bound to the second of the four Xac1, the second of the four Xac1 is covalently bound to the first of the four Xac1 and covalently bound to the third of the four Xac1, the third of the four Xac1 is covalently bound to the second of the four Xac1 and covalently bound to the fourth of the four Xac1, and the fourth of the four Xac1 is covalently bound to the third of the four Xac1 and covalently bound to Z 4 covalent binding;

[0127] Z 4 Selected from H and a chelating agent;

[0128] The condition is: If L 2 is a bond and CT is of formula (CT-II), wherein R CT1 is selected from H and CH3 and R CT2 is (C4-C6) alkyl, then Xaa10 may not be present;

[0129] And wherein the compound of formula (I) may optionally contain a therapeutically active nuclide or a diagnostically active nuclide. BRIEF DESCRIPTION OF THE DRAWINGS

[0130] The following detailed description is further illustrated by reference to the following drawings, which are given by way of example and are not intended to limit the invention, from which further features, embodiments and advantages can be extracted.

[0131] Figure 1(a) is a graphical representation of a PSMA activity inhibition assay.

[0132] Figure 1(b) shows the enzyme inhibition curves of PSM-0374, PSM-0516, PSM-0194, PSM-0416, PSM-0424, and 2-PMPA in a human PSMA activity inhibition assay.

[0133] Figure 2 For display 111 Representative radiochromatogram of In-labeled PSM-0433.

[0134] Figure 3(a)-3(ii) showed that PC3-PIP tumor model in mice 111 % ID / g uptake (biodistribution) of In-labeled compounds (see Example 35).

[0135] Figure 3(a) shows the difference between the two groups at 1 hour, 4 hours and 24 hours after injection. 111 % ID / g uptake of In-PSM-0234.

[0136] Figure 3(b) shows the difference between the two groups at 1 h, 4 h and 24 h after injection. 111 % ID / g uptake of In-PSM-0425.

[0137] Figure 3(c) shows the difference between the two groups at 1 h, 4 h and 24 h after injection. 111 % ID / g uptake of In-PSM-0218.

[0138] Figure 3(d) shows the difference between the two groups at 1 h, 4 h and 24 h after injection. 111 % ID / g uptake of In-PSM-0365.

[0139] Figure 3(e) shows the difference between the two groups at 1 h, 4 h and 24 h after injection. 111 % ID / g uptake of In-PSM-0580.

[0140] Figure 3(f) shows the difference between the two groups at 1 h, 4 h and 24 h after injection. 111 % ID / g uptake of In-PSM-0492.

[0141] Figure 3(g) shows the difference between the two groups at 1 h, 4 h and 24 h after injection. 111 % ID / g uptake of In-PSM-0285.

[0142] Figure 3(h) shows the expression of α-glucose at 1 h, 4 h and 24 h after injection. 111 % ID / g uptake of In-PSM-0237.

[0143] Figure 3(i) shows the difference between the two groups at 1 h, 4 h and 24 h after injection. 111 % ID / g uptake of In-PSM-0428.

[0144] Figure 3(j) shows the expression of α-glucose at 1 h, 4 h, 24 h, 48 h, and 72 h after injection. 111 % ID / g uptake of In-PSM-0283.

[0145] Figure 3(k) shows the expression of α-glucose at 1 h, 4 h, 24 h, 48 h and 72 h after injection. 111 % ID / g uptake of In-PSM-0573.

[0146] Figure 3 (l) shows that 4h and 24h after injection 111 % ID / g uptake of In-PSM-0190.

[0147] Figure 3(m) shows the results at 1h, 4h and 24h after injection. 111 % ID / g uptake of In-PSM-0239.

[0148] Figure 3(n) shows the results at 1h, 4h and 24h after injection. 111 % ID / g uptake of In-PSM-0371.

[0149] Figure 3(o) shows the difference between the two groups at 1 hour, 4 hours and 24 hours after injection. 111 % ID / g uptake of In-PSM-0339.

[0150] Figure 3(p) shows the difference between the two groups at 1 hour, 4 hours and 24 hours after injection. 111 % ID / g uptake of In-PSM-0301.

[0151] Figure 3 (q) shows the 1h, 4h and 24h after injection 111 % ID / g uptake of In-PSM-0243.

[0152] Figure 3(r) shows the expression of α-glucose at 1 h, 4 h, 24 h and 48 h after injection. 111 % ID / g uptake of In-PSM-0199.

[0153] Figure 3(s) shows the results at 1h, 4h, 24h and 48h after injection. 111 % ID / g uptake of In-PSM-0361.

[0154] Figure 3(t) shows the time at 1h, 4h, 24h and 48h after injection 111 % ID / g uptake of In-PSM-0273.

[0155] Figure 3(u) shows the expression of α-glucose at 1h, 4h, 24h, 48h and 72h after injection. 111 % ID / g uptake of In-PSM-0433.

[0156] Figure 3(v) shows the expression of α-glucose at 1 h, 4 h, 24 h, 48 h and 72 h after injection. 111 % ID / g uptake of In-PSM-0534.

[0157] Figure 3 (w) shows the expression of α-glucose at 1 h, 4 h, 24 h, 48 h and 72 h after injection. 111 % ID / g uptake of In-PSM-0269.

[0158] Figure 3(x) shows the expression of α-glucose at 1h, 4h, 24h, 48h and 72h after injection. 111 % ID / g uptake of In-PSM-0267.

[0159] Figure 3(y) shows the expression of α-glucose at 1 h, 4 h, 24 h and 48 h after injection. 111 % ID / g uptake of In-PSM-0481.

[0160] Figure 3(z) shows the expression of α-glucose at 1 h, 4 h, 24 h, 48 h and 72 h after injection. 111 % ID / g uptake of In-PSM-0416.

[0161] Figure 3 (aa) shows the expression of α-glucose at 1 h, 4 h, 24 h and 48 h after injection. 111 % ID / g uptake of In-PSM-0194.

[0162] Figure 3 (bb) shows the results at 1h, 4h, 24h and 48h after injection. 111 % ID / g uptake of In-PSM-0377.

[0163] Figure 3 (cc) shows the expression of α-glucose at 1 h, 4 h, 24 h, 48 h and 72 h after injection. 111 % ID / g uptake of In-PSM-0516.

[0164] Figure 3 (dd) shows the expression of α-glucose at 1 h, 4 h, 24 h, 48 h and 72 h after injection. 111 % ID / g uptake of In-PSM-0467.

[0165] Figure 3 (ee) shows the difference between the two groups at 1h, 4h, 24h, 48h and 72h after injection. 111 % ID / g uptake of In-PSM-0384.

[0166] Figure 3 (ff) shows the expression of α-glucose at 1 h, 4 h, 24 h and 48 h after injection. 111 % ID / g uptake of In-PSM-0449.

[0167] Figure 3 (gg) shows the expression of α-glucose at 1 h, 4 h, 24 h, 48 h and 72 h after injection. 111% ID / g uptake of In-PSM-0241.

[0168] Figure 3 (hh) shows the expression of α-glucose at 1 h, 4 h, 24 h and 48 h after injection. 111 % ID / g uptake of In-PSM-0579.

[0169] Figure 3(ii) shows the expression of α-glucose at 1 h, 4 h, 24 h, 48 h and 72 h after injection. 111 % ID / g uptake of In-PSM-0531.

[0170] Figures 4(a)-4(r) show 111 % ID / g uptake (biodistribution) of In-labeled compounds in the mouse C4-2 tumor model (see Example 35).

[0171] Figure 4(a) shows the difference between the two groups at 1 h, 4 h and 24 h after injection. 111 % ID / g uptake of In-PSM-0285.

[0172] Figure 4(b) shows the difference between the two groups at 1 h, 4 h and 24 h after injection. 111 % ID / g uptake of In-PSM-0428.

[0173] Figure 4(c) shows the difference in the expression of α-glucose at 1 h, 4 h, 24 h and 72 h after injection. 111 % ID / g uptake of In-PSM-0492.

[0174] Figure 4(d) shows the difference between the two groups at 1 h, 4 h and 24 h after injection. 111 % ID / g uptake of In-PSM-0365.

[0175] Figure 4(e) shows the difference between the two groups at 1 h, 4 h and 24 h after injection. 111 % ID / g uptake of In-PSM-0218.

[0176] Figure 4(f) shows the difference between the two groups at 1 h, 4 h and 24 h after injection. 111 % ID / g uptake of In-PSM-0243.

[0177] Figure 4(g) shows the difference between the two groups at 1 h, 4 h and 24 h after injection. 111 % ID / g uptake of In-PSM-0339.

[0178] Figure 4(h) shows the results at 1h, 4h and 24h after injection. 111 % ID / g uptake of In-PSM-0301.

[0179] Figure 4(i) shows the expression of α-glucose at 1 h, 4 h, 24 h and 72 h after injection. 111% ID / g uptake of In-PSM-0283.

[0180] Figure 4(j) shows the expression of α-glucose at 1 h, 4 h, 24 h and 72 h after injection. 111 % ID / g uptake of In-PSM-0433.

[0181] Figure 4(k) shows the difference in the expression of α-glucose at 1 h, 4 h, 24 h and 72 h after injection. 111 % ID / g uptake of In-PSM-0194.

[0182] Figure 4(l) shows the expression of α-glucose at 1 h, 4 h, 24 h, 48 h and 72 h after injection. 111 % ID / g uptake of In-PSM-0345.

[0183] Figure 4(m) shows the expression of α-glucose at 1 h, 4 h, 24 h, 48 h and 72 h after injection. 111 % ID / g uptake of In-PSM-0380.

[0184] Figure 4(n) shows the results at 1h, 4h, 24h and 48h after injection. 111 % ID / g uptake of In-PSM-0483.

[0185] Figure 4(o) shows the expression of α-glucose at 1 h, 4 h, 24 h, 48 h and 72 h after injection. 111 % ID / g uptake of In-PSM-0420.

[0186] Figure 4(p) shows the expression of α-glucose at 1 h, 4 h, 24 h and 48 h after injection. 111 % ID / g uptake of In-PSM-0246.

[0187] Figure 4(q) shows the expression of α-glucose at 1 h, 4 h, 24 h, 48 h and 72 h after injection. 111 % ID / g uptake of In-PSM-0244.

[0188] Figure 4(r) shows the expression of α-glucose at 1 h, 4 h, 24 h and 48 h after injection. 111 % ID / g uptake of In-PSM-0203.

[0189] Figure 5 shows the observed 177 In vivo biodistribution of Lu-PSM-0194 over time (at 4, 24, and 76 hours post-injection) % ID / g, decay-corrected mean values ​​for each organ (blood, kidney (L), kidney (R), liver, tail, and tumor), ROI) are shown.

[0190] Figure 6 For display177 Individual ST1273 tumor volumes over time after Lu-PSM-0194 treatment (dashed line on study day 0 indicates treatment day).

[0191] Figure 7 The amino acid sequence of PSMA is shown (SEQ ID NO: 1). Detailed Description of the Invention

[0193] The present application relates to novel compounds suitable for use as diagnostic and / or pharmaceutically active agents for the diagnosis and / or treatment of prostate cancer and other diseases and conditions mediated by PSMA. The present application provides novel compounds capable of interacting with PSMA, which can deliver therapeutically active or diagnostically active nuclides that can provide for the detection, treatment, and / or management of various diseases associated with one or more PSMA-expressing tumors or cells, including prostate cancer.

[0194] The present application is based on the surprising discovery that the compounds of the present application provide highly specific and potent binding to PSMA. As described herein, the compounds are capable of interacting with PSMA to achieve improved binding affinity and other properties. The compounds of the present invention are surprisingly useful as imaging agents and can be used to deliver radionuclides to tumors.

[0195] The compounds of the present application have one or more advantageous properties, including but not limited to rapid tumor uptake, prolonged tumor retention, rapid clearance of the compound from non-tumor tissues, improved efficacy and / or favorable biodistribution properties, with improved toxicity and side effect profiles. In one embodiment and as preferably used herein, a compound exhibits rapid tumor uptake if, within one hour after administration of the compound to a subject having a tumor, at least 0.1% of the amount of the compound administered to the subject is taken up by the tumor; such tumor uptake is preferably determined by nuclear imaging techniques.

[0196] For effective clinical utilization, PSMA ligand selection should be based on, for example, rapid uptake and persistent localization at the target site, with negligible retention in non-target tissues. Low levels of endogenous PSMA expression are also present in organs such as normal prostate, proximal tubules of the kidney, lacrimal and salivary glands, spleen, liver, mesentery, testis, ovary, and brain (Chakravarty et al., 2018 Am J Nucl Med Mol Imaging, 8(4):247-267), which constitute the range of non-target tissues.

[0197] For diagnosis and / or treatment, the compound of the present application can be complexed with a radionuclide as an α-emitter, a β-emitter, a γ-emitter or a spiral emitter. Radionuclides as α-emitters can destroy tumors while causing very limited damage to surrounding healthy tissues due to the short penetration depth of α particles. Compared with other radionuclide therapies, their high linear energy transfer (LET) gives them improved relative biological effectiveness (RBE). In addition, when the radionuclide targets the specific tumor cells in vivo for emitting α-, they are very effective in destroying tumor metastasis, which is difficult to treat by currently used technology (de Kruijff et al., 2015 Pharmaceuticals, 8, 321-336). However, toxicity is the main limitation of using α-emitters.

[0198] Irradiation of the salivary glands has been reported to be useful for delivering α-emitting radionuclides such as actinium-225 ( 225 Ac) are the major dose-limiting side effects of small molecule PSMA-targeting agents, particularly due to the irreversible nature of xerostomia.

[0199] Compared to known PSMA inhibitors, the compounds of the present invention surprisingly exhibit low binding to human salivary glands.

[0200] In the clinic, α-emitting radionuclides (e.g. 225 Treatment with Ac) has been shown to cause irreversible grade 3 or 4 xerostomia, leading to significant impairment of patients' quality of life and thus representing a dose-limiting side effect of therapeutic use of alpha-emitting small molecule PSMA inhibitors (Tonnesmann et al., 2019, Pharmaceuticals 12, 18). However, PSMA-targeting antibodies have shown no significant uptake in the salivary glands. Although salivary glands are known to have low levels of PSMA, the salivary gland uptake of PSMA-inhibitors detected in clinical studies does not correlate with the relatively low physiological PSMA expression in this tissue, suggesting that binding to the salivary glands is largely nonspecific (Tonnesmann et al., 2019).

[0201] The PSMA ligands disclosed herein are surprisingly suitable as carriers for therapeutic α-emitters because they can provide effective treatment for diseases associated with one or more PSMA-expressing tumors or cells, including prostate cancer, with reduced salivary gland uptake. This allows for the administration of such compounds at higher doses, potentially leading to improved response rates and better tumor control.

[0202] The compounds of the present application have a favorable uptake ratio between tumor and non-tumor tissues (eg, salivary glands, kidneys or other non-tumor tissues).

[0203] In certain embodiments, the favorable tumor and non-tumor tissue uptake of the compounds of the present invention allows for the delivery of radionuclides at doses that can reduce tumor growth or partially or completely destroy tumors while minimizing side effects. In certain embodiments, due to their favorable uptake ratios of tumor and non-tumor targets, the compounds of the present application are surprisingly able to overcome the undesirable side effect of severe dry mouth associated with known PSMA-inhibitors. In certain embodiments, the compounds of the present application can advantageously provide effective treatment for diseases associated with one or more PSMA-expressing tumors or cells, including prostate cancer, and can allow for the administration of higher doses, potentially leading to improved response rates and better tumor control. In certain embodiments, the compounds of the present application can advantageously maximize therapeutic efficacy while minimizing adverse side effects.

[0204] In some embodiments, the compounds of the present application can be advantageously used in methods for identifying subjects or for selecting subjects from a group of subjects or for stratifying a group of subjects, wherein the subjects may or may not respond to treatment for a disease, wherein the method comprises a method for diagnosing using the compounds according to the present application. In certain embodiments, such methods can advantageously optimize drug therapy, including minimizing risk and maximizing efficacy, for example, by helping healthcare professionals identify subjects who may benefit most from a given therapy and avoiding unnecessary treatment.

[0205] The present application is further described herein, including in the following embodiments.

[0206] Embodiment 1. A compound of formula (I) or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof,

[0207]

[0208] in

[0209] X is selected from a bond and -CH2-;

[0210] Z 1 Selected from chelating agents and NT;

[0211] NT is selected from the group consisting of H, Ac, Hex, HPA, HO-succinyl, SaPr, Iva, HYDAc, Bio, nBuCAyl, AF488Ahx, and Hib;

[0212] L 1 Selected from a bond and -(Xaa1) k -,

[0213] k is selected from 1, 2 and 3,

[0214] Xaa1 are each independently an amino acid residue, preferably, the amino acid residue is selected from α-amino acid residue, β-amino acid residue, γ-amino acid residue, δ-amino acid residue, ε-amino acid residue, ω-amino acid residue and an amino acid residue of formula (YI),

[0215]

[0216] g is an integer selected from 0-23,

[0217] in,

[0218] If k=1, then Xaa1 and Z 1 covalently bound to and covalently bound to Xaa2,

[0219] If k=2, then the first of the two Xaa1 and Z 1 covalently bound to and covalently bound to the second of the two Xaa1s, and the second of the two Xaa1s is covalently bound to the first of the two Xaa1s and covalently bound to Xaa2,

[0220] If k=3, then the first of the three Xaa1 and Z 1 covalently bound to and covalently bound to the second of the three Xaa1s, the second of the three Xaa1s is covalently bound to the first of the three Xaa1s and covalently bound to the third of the three Xaa1s, and the third of the three Xaa1s is covalently bound to the second of the three Xaa1s and covalently bound to Xaa2;

[0221] When L 1 When Z is a key, 1 is NT;

[0222] Xaa2 is selected from formula (II) and formula (III):

[0223]

[0224] where R 2a Selected from H, (C1-C6) alkyl and CH2R 2g ;

[0225] R 2g Selected from OH and CO2H;

[0226] R 2b selected from H and (C1-C6)alkyl;

[0227] Or, R2a and R 2b can form a 5- or 6-membered carbocyclic or heterocyclic ring together,

[0228] R 2c selected from H and CH3;

[0229] R 2d selected from H, F and OH;

[0230] R 2e Selected from H and F;

[0231] R 2f selected from H and CH3;

[0232] The condition is that when L 1 Xaa2 may not be present when it is a bond and NT is Hib;

[0233] Xaa3 is selected from formula (IV):

[0234]

[0235] where R 3a is selected from aryl, (C5-C6)heteroaryl, indol-3-yl, 6-chloro-1H-indol-3-yl and -S-CH2-phenyl; and wherein R 3a The aryl or heteroaryl ring is optionally substituted with 1, 2 or 3 substituents independently selected from halogen, (C1-C6)alkyl, CN, OH and -O(C1-C3)alkyl, wherein the (C1-C6)alkyl may be optionally substituted with one or more fluorine;

[0236] R 3b selected from H and CH3;

[0237] h is selected from 1 and 2;

[0238] Xaa5 is selected from the group consisting of Formula (Va), Formula (Vb), Hgn, Lys, Nle, Tap, Aph, and Gln:

[0239]

[0240] where R 5a Selected from H, (C1-C6) alkyl, Ac, C(=NR 5d )NR 5e R 5f and Bio;

[0241] R 5d selected from H and CH3;

[0242] R 5e and R 5f independently selected from H and (C1-C6)alkyl;

[0243] R 5b selected from H and (C1-C6)alkyl;

[0244] R 5c selected from H and CH3;

[0245] m is selected from 2, 3, 4 and 5; and

[0246] R 5g 、R 5h and R 5i independently selected from (C1-C6)alkyl;

[0247] Xaa6 is selected from Formula (VI), Formula (VII), Nle and arg:

[0248]

[0249] where R 6a Selected from H, C(=NR 6e )NR 6f R 6g 、C(=O)R 6h and pyridyl;

[0250] R 6e selected from H and CH3;

[0251] R 6f Selected from H, (C1-C6) alkyl, Ac, NO2 and C(=O)NR 6i R 6j ;

[0252] R 6i and R 6j independently selected from H and (C1-C2)alkyl;

[0253] R 6g selected from H and (C1-C6)alkyl;

[0254] Or, R 6e and R 6f They can form a 5- or 6-membered heterocyclic ring.

[0255] R 6h Selected from (C1-C6) alkyl, NR 6k R 6m and NR 6n C(=NR 6p )NR 6q R 6r ;

[0256] R 6k and R 6m independently selected from H and (C1-C6)alkyl;

[0257] R 6n and R 6p independently selected from H and CH3;

[0258] R 6q and R 6r independently selected from H and (C1-C6)alkyl;

[0259] R 6b selected from H and (C1-C6)alkyl;

[0260] R 6c selected from H and CH3;

[0261] n is selected from 1, 2, 3 and 4;

[0262] R 6d Selected from NR 6s C(=NR 6t )NR 6u R 6v , OH and NR 6w R 6x ;

[0263] R 6s and R 6t independently selected from H and CH3;

[0264] R 6u 、R 6v 、R 6w and R 6x independently selected from H and (C1-C6)alkyl; and

[0265] q is selected from 2, 3 and 4;

[0266] Xaa7 is an amino acid residue, wherein the amino acid residue is preferably selected from Formula (VIII), Formula (IX), Formula (X), Formula (XI), Dtc and Oic:

[0267]

[0268] where R 7a Selected from H, (C1-C6) alkyl and (CH2) t R 7g ;

[0269] R 7g Selected from OH, CO2H and NR 7h R 7i ;

[0270] R 7h and R 7i independently selected from H and (C1-C6)alkyl;

[0271] t is selected from 1, 2, 3 and 4;

[0272] R 7b selected from H and (C1-C6)alkyl;

[0273] Or, R 7a and R 7b can form a 5- or 6-membered carbocyclic or heterocyclic ring together,

[0274] R 7c selected from H and CH3;

[0275] R 7d selected from H, F and OH;

[0276] R 7e Selected from H and F;

[0277] R 7f selected from H and CH3;

[0278] u is selected from 2, 3 and 4;

[0279] L 3 Selected from bonds and -(Xab1) v -,

[0280] Wherein v is selected from 1, 2 and 3,

[0281] Xab1 is each independently an amino acid residue, preferably, the amino acid residue is selected from α-amino acid residue, β-amino acid residue, γ-amino acid residue, δ-amino acid residue, ε-amino acid residue, ω-amino acid residue and an amino acid residue of formula (YI),

[0282] If v=1, then Xab1 and Z 3 covalently bound to the side chain amino functional group of formula (X) or formula (XI),

[0283] If v=2, the first of the two Xab1 and Z 3 covalently bound to the second of the two Xab1, and the second of the two Xab1 is covalently bound to the first of the two Xab1 and covalently bound to the side chain amino functional group of formula (X) or formula (XI),

[0284] If v=3, the first of the three Xab1 and Z 3covalently bound to the second of the three Xab1s and covalently bound to the third of the three Xab1s, and the third of the three Xab1s is covalently bound to the second of the three Xab1s and covalently bound to the side chain amino functional group of formula (X) or formula (XI);

[0285] Z 3 Selected from H and a chelating agent;

[0286] Xaa8 is an α-amino acid residue, wherein the α-nitrogen atom of Xaa8 is unsubstituted or optionally substituted with CH3;

[0287] Xaa10 is formula (XII):

[0288]

[0289] in:

[0290] R 10a Selected from (C1-C6)alkyl;

[0291] R 10b selected from H and (C1-C6)alkyl;

[0292] Or, R 10a and R 10b can form a 5- or 6-membered carbocyclic or heterocyclic ring together,

[0293] R 10c selected from H and CH3;

[0294] L 2 Selected from: bond and -Xaa11-(Xaa12) s -, so that Xaa11 and Xaa10 are covalently bound;

[0295] Xaa11 is an amino acid residue, wherein the amino acid residue is preferably selected from the group consisting of an α-amino acid residue, a β-amino acid residue, a γ-amino acid residue, a δ-amino acid residue, an ε-amino acid residue, an ω-amino acid residue and an amino acid residue of formula (YI);

[0296] s is selected from the group consisting of 0, 1, 2, 3, 4, and 5; and

[0297] Xaa12 are each independently an amino acid residue, wherein the amino acid residue is preferably selected from the group consisting of an α-amino acid residue, a β-amino acid residue, a γ-amino acid residue, a δ-amino acid residue, an ε-amino acid residue, an ω-amino acid residue and an amino acid residue of formula (YI),

[0298] If s=0, then Xaa11 and Z 2covalently bound,

[0299] If s=1, Xaa12 is covalently bound to Xaa11 and to Z 2 covalently bound,

[0300] If s=2, the first of the two Xaa12 is covalently bound to Xaa11 and covalently bound to the second of the two Xaa12, and the second of the two Xaa12 is covalently bound to the first of the two Xaa12 and covalently bound to Z 2 covalently bound,

[0301] If s=3, the first of the three Xaa12 is covalently bound to Xaa11 and covalently bound to the second of the three Xaa12, the second of the three Xaa12 is covalently bound to the first of the three Xaa12 and covalently bound to the third of the three Xaa12, and the third of the three Xaa12 is covalently bound to the second of the three Xaa12 and covalently bound to Z. 2 covalently bound,

[0302] If s=4, the first of the four Xaa12 is covalently bound to Xaa11 and covalently bound to the second of the four Xaa12, the second of the four Xaa12 is covalently bound to the first of the four Xaa12 and covalently bound to the third of the four Xaa12, the third of the four Xaa12 is covalently bound to the second of the four Xaa12 and covalently bound to the fourth of the four Xaa12, and the fourth of the four Xaa12 is covalently bound to the third of the four Xaa12 and covalently bound to Z. 2 covalently bound,

[0303] If s=5, the first of the five Xaa12 is covalently bound to Xaa11 and covalently bound to the second of the five Xaa12, the second of the five Xaa12 is covalently bound to the first of the five Xaa12 and covalently bound to the third of the five Xaa12, the third of the five Xaa12 is covalently bound to the second of the five Xaa12 and covalently bound to the fourth of the five Xaa12, the fourth of the five Xaa12 is covalently bound to the third of the five Xaa12 and covalently bound to the fifth of the five Xaa12, and the fifth of the five Xaa12 is covalently bound to the fourth of the five Xaa12 and covalently bound to Z 2 covalent binding;

[0304] Z 2An α-amino acid residue selected from CT, XDa-chelating agents and formula (CT-I):

[0305]

[0306] CT is selected from the group consisting of formula (CT-II), formula (CT-III), AF488N3K-NH2, OH, and Throl-OH:

[0307]

[0308] in:

[0309] R CT1 selected from H and CH3;

[0310] R CT2 selected from H and (C1-C6)alkyl;

[0311] R CT3 and R CT4 are each independently selected from H and CH3;

[0312] R CT5 selected from H and (C1-C6)alkyl;

[0313] x is selected from 2 to 10;

[0314] XDa is a diamine, wherein the diamine is preferably selected from en and Ape;

[0315] w is selected from 1, 2, 3, 4, 5 and 6;

[0316] L 4 Selected from bonds and -(Xac1) y -,

[0317] in:

[0318] y is selected from 0, 1, 2 and 3,

[0319] Xac1 is each independently an amino acid residue, preferably, the amino acid residue is selected from α-amino acid residue, β-amino acid residue, γ-amino acid residue, δ-amino acid residue, ε-amino acid residue, ω-amino acid residue and an amino acid residue of formula (YI),

[0320] If y=0, the side chain amino functional group of the α-amino acid residue of formula (CT-I) is 4 covalently bound,

[0321] If y=1, Xac1 is covalently bound to the side chain amino functional group of the α-amino acid residue of formula (CT-I) and to Z 4 covalently bound,

[0322] If y=2, the first of the two Xac1 is covalently bound to the side chain amino functional group of the α-amino acid residue of formula (CT-I) and covalently bound to the second of the two Xac1, and the second of the two Xac1 is covalently bound to the first of the two Xac1 and to Z 4 covalently bound,

[0323] If y=3, the first of the three Xac1 is covalently bound to the side chain amino functional group of the α-amino acid residue of formula (CT-I) and covalently bound to the second of the three Xac1, the second of the three Xac1 is covalently bound to the first of the three Xac1 and covalently bound to the third of the three Xac1, and the third of the three Xac1 is covalently bound to the second of the three Xac1 and covalently bound to Z 4 covalently bound,

[0324] If y=4, the first of the four Xac1 is covalently bound to the side chain amino functional group of the α-amino acid residue of formula (CT-I) and covalently bound to the second of the four Xac1, the second of the four Xac1 is covalently bound to the first of the four Xac1 and covalently bound to the third of the four Xac1, the third of the four Xac1 is covalently bound to the second of the four Xac1 and covalently bound to the fourth of the four Xac1, and the fourth of the four Xac1 is covalently bound to the third of the four Xac1 and covalently bound to Z 4 covalent binding;

[0325] Z 4 Selected from H and a chelating agent;

[0326] The condition is: If L 2 is a bond and CT is of formula (CT-II), wherein R CT1 is selected from H and CH3 and R CT2 is (C4-C6) alkyl, then Xaa10 may not be present;

[0327] And wherein the compound of formula (I) may optionally contain a therapeutically active nuclide or a diagnostically active nuclide.

[0328] Embodiment 2. A compound of formula (I) or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof,

[0329]

[0330] in

[0331] X is selected from a bond and -CH2-;

[0332] Z 1 Selected from chelating agents and NT;

[0333] NT is selected from the group consisting of H, Ac, Hex, HPA, HO-succinyl, SaPr, Iva, HYDAc, Bio, nBuCAyl, AF488Ahx, and Hib;

[0334] L 1 Selected from bonds and –(Xaa1) k –

[0335] k is selected from 1, 2, and 3;

[0336] in,

[0337] If k=1, then Xaa1 and Z 1 covalently bound to and covalently bound to Xaa2,

[0338] If k=2, the first of the two Xaa1 is covalently bound to Z1 and covalently bound to the second of the two Xaa1, and the second of the two Xaa1 is covalently bound to the first of the two Xaa1 and covalently bound to Xaa2,

[0339] If k=3, the first of the three Xaa1s is covalently bound to Z1 and covalently bound to the second of the three Xaa1s, the second of the three Xaa1s is covalently bound to the first of the three Xaa1s and covalently bound to the third of the three Xaa1s, and the third of the three Xaa1s is covalently bound to the second of the three Xaa1s and covalently bound to Xaa2;

[0340] When L 1 When Z is a key, 1 is NT;

[0341] Each Xaa1 is independently selected from Thr, Ala, Ser, Pamp, Leu, Ile, Nmt, Pamb, Ahx, APAc, PPAc, Bal, Cmp, Pab, O2Oc, Met and Ttds;

[0342] Xaa2 is selected from the group consisting of Aib, Ala, Amd, Ams, amd, ams, Deg, Nmg, Pam, and Pro; provided that when L 1 Xaa2 may not be present when it is a bond and NT is Hib;

[0343] Xaa3 is selected from Phe, Nmf, 1Ni, 2Ni, 6Clw, Cys(Bzl), Hfe, Trp, Mpa, Opa, and Ppa, wherein Phe, Nmf, and Hfe are optionally substituted with 1 or 2 substituents independently selected from halogen, CH3, CN, CF3, and OH;

[0344] Xaa5 is selected from the group consisting of Formula (Va), Formula (Vb), Hgn, Lys, Nle, Tap, Aph, and Gln:

[0345]

[0346] where R 5a Selected from H, (C1-C6) alkyl, Ac, C(=NR 5d )NR 5e R 5f and Bio;

[0347] R 5d selected from H and CH3;

[0348] R 5e and R 5f independently selected from H and (C1-C6)alkyl;

[0349] R 5b selected from H and (C1-C6)alkyl;

[0350] R 5c selected from H and CH3;

[0351] m is selected from 2, 3, 4 and 5; and

[0352] R 5g 、R 5h and R 5i independently selected from (C1-C6)alkyl;

[0353] Xaa6 is selected from Formula (VI), Formula (VII), Nle and arg:

[0354]

[0355] where R 6a Selected from H, C(=NR 6e )NR 6f R 6g 、C(=O)R 6h and pyridyl;

[0356] R 6e selected from H and CH3;

[0357] R 6f Selected from H, (C1-C6) alkyl, Ac, NO2 and C(=O)NR6i R 6j ;

[0358] R 6i and R 6j independently selected from H and (C1-C2)alkyl;

[0359] R 6g selected from H and (C1-C6)alkyl;

[0360] Or, R 6e and R 6f They can form a 5- or 6-membered heterocyclic ring.

[0361] R 6h Selected from (C1-C6) alkyl, NR 6k R 6m and NR 6n C(=NR 6p )NR 6q R 6r ;

[0362] R 6k and R 6m independently selected from H and (C1-C6)alkyl;

[0363] R 6n and R 6p independently selected from H and CH3;

[0364] R 6q and R 6r independently selected from H and (C1-C6)alkyl;

[0365] R 6b selected from H and (C1-C6)alkyl;

[0366] R 6c selected from H and CH3;

[0367] n is selected from 1, 2, 3 and 4;

[0368] R 6d Selected from NR 6s C(=NR 6t )NR 6u R 6v , OH and NR 6w R 6x ;

[0369] R 6s and R 6t independently selected from H and CH3;

[0370] R 6u 、R 6v 、R 6w and R6x independently selected from H and (C1-C6)alkyl; and

[0371] q is selected from 2, 3 and 4;

[0372] Xaa7 is selected from Formula (VIII), Formula (IX), Formula (X), Formula (XI), Dtc and Oic:

[0373]

[0374] where R 7a Selected from H, (C1-C6) alkyl and (CH2) t R 7g ;

[0375] R 7g Selected from OH, CO2H and NR 7h R 7i ';

[0376] R 7h and R 7i independently selected from H and (C1-C6)alkyl;

[0377] t is selected from 1, 2, 3 and 4;

[0378] R 7b selected from H and (C1-C6)alkyl;

[0379] Or, R 7a and R 7b can form a 5- or 6-membered carbocyclic or heterocyclic ring together,

[0380] R 7c selected from H and CH3;

[0381] R 7d selected from H, F and OH;

[0382] R 7e Selected from H and F;

[0383] R 7f selected from H and CH3;

[0384] u is selected from 2, 3 and 4;

[0385] L 3 Selected from bonds and -(Xab1) v ;

[0386] v is selected from 1, 2 and 3;

[0387] Xab1 is each independently selected from Ttds, Pamb, APAc, O2Oc, Ahx, Pab and Cmp;

[0388] Among them, if v=1, then Xab1 and Z 3 covalently bound to the side chain amino functional group of formula (X) or formula (XI),

[0389] If v=2, the first of the two Xab1 and Z 3 covalently bound to the second of the two Xab1, and the second of the two Xab1 is covalently bound to the first of the two Xab1 and covalently bound to the side chain amino functional group of formula (X) or formula (XI),

[0390] If v=3, the first of the three Xab1 and Z 3 covalently bound to the second of the three Xab1s and covalently bound to the third of the three Xab1s, and the third of the three Xab1s is covalently bound to the second of the three Xab1s and covalently bound to the side chain amino functional group of formula (X) or formula (XI);

[0391] Z 3 Selected from H and a chelating agent;

[0392] Xaa8 is an α-amino acid residue, wherein the α-nitrogen atom of Xaa8 is unsubstituted or optionally substituted with CH3;

[0393] Xaa10 is formula (XII)

[0394]

[0395] in

[0396] R 10a Selected from (C1-C6)alkyl;

[0397] R 10b selected from H and CH3;

[0398] R 10c selected from H and CH3;

[0399] L 2 Selected from: bond and -Xaa11-(Xaa12) s -, so that Xaa11 and Xaa10 are covalently bound;

[0400] Xaa11 is selected from Thr, Ala, Bal, Gab, Gln, Glu, Gly, Leu, Nmt, Phe, Pro and Trp;

[0401] s is selected from the group consisting of 0, 1, 2, 3, 4, and 5; and

[0402] Each Xaa12 is independently selected from Asp, asp, Ala, Gab, Ttds, Pamb, Cmp, O2Oc, APAc, Gly, Ser, Lys(Bio) and Pab;

[0403] If s=0, then Xaa11 and Z 2 covalently bound,

[0404] If s=1, Xaa12 is covalently bound to Xaa11 and to Z 2 covalently bound,

[0405] If s=2, the first of the two Xaa12 is covalently bound to Xaa11 and covalently bound to the second of the two Xaa12, and the second of the two Xaa12 is covalently bound to the first of the two Xaa12 and covalently bound to Z 2 covalently bound,

[0406] If s=3, the first of the three Xaa12 is covalently bound to Xaa11 and covalently bound to the second of the three Xaa12, the second of the three Xaa12 is covalently bound to the first of the three Xaa12 and covalently bound to the third of the three Xaa12, and the third of the three Xaa12 is covalently bound to the second of the three Xaa12 and covalently bound to Z. 2 covalently bound,

[0407] If s=4, the first of the four Xaa12 is covalently bound to Xaa11 and covalently bound to the second of the four Xaa12, the second of the four Xaa12 is covalently bound to the first of the four Xaa12 and covalently bound to the third of the four Xaa12, the third of the four Xaa12 is covalently bound to the second of the four Xaa12 and covalently bound to the fourth of the four Xaa12, and the fourth of the four Xaa12 is covalently bound to the third of the four Xaa12 and covalently bound to Z. 2 covalently bound,

[0408] If s=5, the first of the five Xaa12 is covalently bound to Xaa11 and covalently bound to the second of the five Xaa12, the second of the five Xaa12 is covalently bound to the first of the five Xaa12 and covalently bound to the third of the five Xaa12, the third of the five Xaa12 is covalently bound to the second of the five Xaa12 and covalently bound to the fourth of the five Xaa12, the fourth of the five Xaa12 is covalently bound to the third of the five Xaa12 and covalently bound to the fifth of the five Xaa12, and the fifth of the five Xaa12 is covalently bound to the fourth of the five Xaa12 and covalently bound to Z 2 covalent binding;

[0409] Z 2 Selected from CT, -en-chelating agent, -Ape-chelating agent and formula (CT-I)

[0410]

[0411] CT is selected from NH2, en, en(Me)2, en(Me), NHBu, NHnPen, AF488N3K-NH2, OH and Throl-OH;

[0412] w is selected from 2, 3 and 4;

[0413] L 4 is selected from the group consisting of a bond, Ttds, Pamb, APAc, O2Oc, Ahx, Pab, and Cmp;

[0414] Z 4 It is a chelating agent;

[0415] The condition is: If L 2 is a bond and CT is NHnPen, then Xaa10 may not be present;

[0416] And wherein the compound of formula (I) may optionally contain a therapeutically active nuclide or a diagnostically active nuclide.

[0417] Embodiment 3. The compound of any one of Embodiments 1 and 2, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Z 1 、Z 2 、Z 3 and Z 4 Only 1 of the 10 contains a chelating agent.

[0418] Embodiment 4. The compound of any one of Embodiments 1, 2 and 3, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein X is a bond.

[0419] Embodiment 5. The compound of any one of Embodiments 1, 2 and 3, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein X is CH2.

[0420] Embodiment 6. The compound of any one of Embodiments 1, 2, 3, 4 and 5, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein

[0421] Z 2 is CT; and

[0422] Xaa7 is selected from Formula (VIII), Formula (IX), Dtc and Oic.

[0423] Embodiment 7. The compound of embodiment 6 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Z 1 It is a chelating agent.

[0424] Embodiment 8. The compound of any one of Embodiments 6 and 7, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein

[0425] L 1 -(Xaa1) k -; and wherein k is selected from 1 and 2.

[0426] Embodiment 9. The compound of any one of Embodiments 6, 7 and 8, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein k is 2, and L 1 Formula (XIII):

[0427] -Xaa1 b -Xaa1 a -,

[0428] (XIII)

[0429] Among them, Xaa1 a Covalently bound to Xaa2;

[0430] Xaa1 a is selected from Thr, Ile, and Leu; and

[0431] Xaa1 b Selected from Cmp, Ttds, Pamb, Ahx, APAc, Bal, O2Oc and Pab.

[0432] Embodiment 10. The compound of Embodiment 9 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa1 a For Thr.

[0433] Embodiment 11. The compound of any one of Embodiments 9 and 10, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa1 b is Cmp.

[0434] Embodiment 12. The compound of any one of Embodiments 6, 7 and 8, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein k is 1 and Xaa1 is selected from Cmp, Pamb, Bal, Pab, Ahx, APAc, Thr, Pamp and PPAc.

[0435] Embodiment 13. The compound of Embodiment 12, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa1 is Pamb.

[0436] Embodiment 14. The compound of any one of Embodiments 6, 7, 8, 9, 10, 11, 12 and 13, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein L 2 Selected from bonds and -Xaa11-(Xaa12) s -; and s is selected from 0 and 1.

[0437] Embodiment 15. The compound of embodiment 14 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein L 2 -Xaa11-(Xaa12) s -;

[0438] s is selected from 0 and 1; and

[0439] Xaal 1 is selected from the group consisting of Thr, Bal, Gln, Phe, Gab, Nmt, Gly, Leu, Trp, Glu, and Pro.

[0440] Embodiment 16. The compound of any one of Embodiments 14 and 15, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa11 is selected from Thr and Bal.

[0441] Embodiment 17. The compound of Embodiment 16, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa11 is Thr.

[0442] Embodiment 18. The compound of Embodiment 16, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa11 is Bal.

[0443] Embodiment 19. The compound of any one of Embodiments 15, 16, 17 and 18, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein s is 0.

[0444] Embodiment 20. The compound of any one of Embodiments 14, 15, 16, 17 and 18, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein s is 1; and Xaa12 is Asp.

[0445] Embodiment 21. The compound of embodiment 14 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein L 2 Yes key.

[0446] Embodiment 22. The compound of any one of Embodiments 14, 15, 16, 17, 18, 19, 20 and 21, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein CT is selected from NH2, en, en(Me), en(Me)2, NHBu, Throl-OH and OH.

[0447] Embodiment 23. The compound of Embodiment 22, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein CT is NH2.

[0448] Embodiment 24. The compound of any one of Embodiments 6, 7, 8, 9, 10, 11, 12, 13 and 14, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein L 2 -Z 2 Selected from Thr-NH2, Bal-NH2, Glu-NH2, Pro-NH2, Gln-NH2, Trp-NH2, Leu-NH2, Gly-NH2, Nmt-NH2, Gab-NH2, Phe-NH2, Throl-OH and Thr-OH.

[0449] Embodiment 25. The compound of embodiment 24 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein L 2 -Z 2 Selected from Thr-NH2 and Bal-NH2.

[0450] Embodiment 26. The compound of embodiment 25 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein L 2 -Z 2 It is Thr-NH2.

[0451] Embodiment 27. The compound of embodiment 25 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein L 2 -Z 2 It is Bal-NH2.

[0452] Embodiment 28. The compound of any one of Embodiments 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26 and 27, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa7 is selected from Formula (VIII), Formula (IX), Dtc and Oic, wherein

[0453] R 7a Selected from H, (C1-C6) alkyl and (CH2) t R 7g ;

[0454] t is selected from 1 and 2; and

[0455] R 7g Selected from OH, CO2H and NH2.

[0456] Embodiment 29. The compound of Embodiment 28, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa7 is selected from Aib, Ala, Glu, Pro, Dfp, glu, Amd, 4Tfp, Pam, Deg, Nmg, Ams, ams, amd, Dtc and Oic.

[0457] Embodiment 30. The compound of embodiment 28, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa7 is selected from formula (VIII), and wherein

[0458] R 7a is selected from H, (C1-C2)alkyl, CH2OH, CH2CO2H and CH2CH2CO2H;

[0459] R 7b selected from H and (C1-C2)alkyl; and

[0460] R 7c It’s H.

[0461] Embodiment 31. The compound of any one of Embodiments 28, 29 and 30, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa7 is selected from Aib and Ala.

[0462] Embodiment 32. The compound of any one of Embodiments 28, 29, 30 and 31, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa7 is Aib.

[0463] Embodiment 33. The compound of any one of Embodiments 28, 29, 30 and 31, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa7 is Ala.

[0464] Embodiment 34. The compound of any one of Embodiments 1, 2, 3, 4 and 5, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein

[0465] Z 1 is NT, and

[0466] Xaa7 is selected from Formula (VIII), Formula (IX), Dtc and Oic.

[0467] Embodiment 35. The compound of embodiment 34 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Z 2 Selected from en-chelating agents, -Ape-chelating agents and formula (CT-I), wherein if Z 2 For formula (CT-I), then Z 4 For the chelating agent.

[0468] Embodiment 36. The compound of any one of Embodiments 34 and 35, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein

[0469] L 1 Selected from a bond and (Xaa1) k ;and

[0470] k is selected from 1 and 2.

[0471] Embodiment 37. The compound of embodiment 36, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein k is 2 and L 1 Formula (XIII)

[0472] -Xaa1 b -Xaa1 a -,

[0473] (XIII)

[0474] Among them, Xaa1 a covalently bound to Xaa2 of formula (I);

[0475] Xaa1 a is Thr; and

[0476] Xaa1 b It is Met or Cmp.

[0477] Embodiment 38. The compound of embodiment 37, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa1 b It's the Met.

[0478] Embodiment 39. The compound of any one of Embodiments 37 and 38, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein NT is selected from H, Ac and nBuCAyl.

[0479] Embodiment 40. The compound of Embodiment 39, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein NT is Ac.

[0480] Embodiment 41. The compound of Embodiment 36, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein k is 1 and Xaa1 is selected from Thr, Ala, Pamp and Ser.

[0481] Embodiment 42. The compound of any one of Embodiments 37 and 38, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa1 is Thr.

[0482] Embodiment 43. The compound of any one of Embodiments 41 and 42, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa1 is selected from Thr and Pamp; and NT is selected from Ac, nBuCAyl and Hex.

[0483] Embodiment 44. The compound of Embodiment 43, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa1 is Thr and NT is Ac.

[0484] Embodiment 45. The compound of embodiment 36 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein L 1 It is a key.

[0485] Embodiment 46. The compound of Embodiment 45, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein NT is selected from Ac, HPA, HYDAc, Iva, SaPr, and HO-succinyl.

[0486] Embodiment 47. The compound of Embodiment 46, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein NT is Ac.

[0487] Embodiment 48. The compound of any one of Embodiments 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46 and 47, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein

[0488] L 2 Yes -Xaa11-(Xaa12) s -;and

[0489] s is selected from 0, 1 and 2.

[0490] Embodiment 49. The compound of embodiment 48 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Z 2 Formula (CT-I).

[0491] Embodiment 50. The compound of any one of Embodiments 48 and 49, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa11 is Thr.

[0492] Embodiment 51. The compound of any one of Embodiments 48, 49 and 50, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein L 2 for

[0493] -Xaa11-(Xaa12) s ; s is 1; and

[0494] Xaa12 is selected from the group consisting of Asp, Cmp, Ttds, Pamb, O2Oc, APAc and Pab.

[0495] Embodiment 52. The compound of Embodiment 51, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa11 is Thr and Xaa12 is Cmp.

[0496] Embodiment 53. The compound of any one of Embodiments 48, 49 and 50, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein L 2 -Xaa11-(Xaa12) s ; and s is 2; and L 2 Has the following structure:

[0497] -Xaa11-Xaa12 a -Xaa12 b -;in

[0498] Xaa12 a is selected from the group consisting of Asp, Cmp, Ttds, Pamb, O2Oc, APAc, and Pab; and

[0499] Xaa12 b It’s Ttds.

[0500] Embodiment 54. The compound of embodiment 53, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa11 is Thr, Xaa12 a Asp, and Xaa12 b For Ttds.

[0501] Embodiment 55. The compound of any one of Embodiments 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47 and 48, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Z 2 Selected from -en-chelating agents and -Ape-chelating agents.

[0502] Embodiment 56. The compound of embodiment 55, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Z 2 It is an en-chelating agent.

[0503] Embodiment 57. The compound of any one of Embodiments 55 and 56, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein L 2 Is a key or Xaa11.

[0504] Embodiment 58. The compound of embodiment 57 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein L 2 is the key.

[0505] Embodiment 59. The compound of embodiment 57 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein L 2 is Xaa11 and Xaa11 is Thr.

[0506] Embodiment 60. The compound of embodiment 55, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Z 2 For -Ape- chelating agent, L 2 is -Xaa11-; and Xaa11 is Thr.

[0507] Embodiment 61. The compound of any one of Embodiments 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59 and 60, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa7 is selected from Formula (VIII), Formula (IX), Dtc and Oic, wherein

[0508] R 7a Selected from H, (C1-C6) alkyl and (CH2) t R 7g ;

[0509] R 7g Selected from OH and CO2H;

[0510] t is selected from 1 and 2; and

[0511] R 7b is selected from H and (C1-C6)alkyl.

[0512] Embodiment 62. The compound of Embodiment 61, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa7 is selected from Aib, Ala, Glu, Pro, Dfp, glu, Amd, 4Tfp, Pam, Deg, Nmg, Ams, ams, amd, Dtc and Oic.

[0513] Embodiment 63. The compound of Embodiment 61, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa7 is Formula (VIII), and wherein

[0514] R 7a is selected from H, (C1-C2)alkyl, CH2OH, CH2CO2H and CH2CH2CO2H;

[0515] R 7b selected from H and (C1-C2)alkyl; and

[0516] R 7c It’s H.

[0517] Embodiment 64. The compound of any one of Embodiments 61, 62 and 63, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa7 is selected from Ala and Aib.

[0518] Embodiment 65. The compound of any one of Embodiments 61, 62, 63 and 64, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa7 is Aib.

[0519] Embodiment 66. The compound of any one of Embodiments 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64 and 65, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa7 is Ala.

[0520] Embodiment 67. The compound of any one of Embodiments 1, 2, 3, 4 and 5, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa7 is selected from Formula (X) and Formula (XI);

[0521] Z 3 It is a chelating agent;

[0522] Z 1 is NT; and

[0523] Z 2 It's CT.

[0524] Embodiment 68. The compound of embodiment 67 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein

[0525] L 1 Selected from a bond and -(Xaa1) k -; and k is 1.

[0526] Embodiment 69. The compound of Embodiment 68, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa1 is Thr.

[0527] Embodiment 70. The compound of embodiment 68 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein L 1 Yes key.

[0528] Embodiment 71. The compound of any one of Embodiments 67, 68, 69 and 70, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein NT is selected from Ac, SaPr, Iva and HPA.

[0529] Embodiment 72. The compound of Embodiment 71, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein NT is Ac.

[0530] Embodiment 73. The compound of any one of Embodiments 67, 68, 69, 70, 71 and 72, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein L 2 Selected from bonds and -Xaa11-(Xaa12) s -, where s is selected from 0 and 1.

[0531] Embodiment 74. The compound of Embodiment 73, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein Xaa11 is selected from Thr, Gln, Phe, Gab, Nmt, Bal, Gly, Leu, Trp, Glu, and Pro.

[0532] Embodiment 75. The compound of any one of Embodiments 73 and 74, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa11 is Thr.

[0533] Embodiment 76. The compound of any one of Embodiments 73, 74 and 75, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein s is 1; and Xaa12 is Asp.

[0534] Embodiment 77. The compound of any one of Embodiments 73, 74, 75 and 76, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein CT is NH2.

[0535] Embodiment 78. The compound of any one of Embodiments 67, 68, 69, 70, 71, 72, 73, 74, 75, 76 and 77, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa7 is selected from Lys and Apc, wherein the ε-nitrogen atom of Lys or the γ-nitrogen atom of Apc is attached to a chelator, wherein an optional linker is inserted between Apc or Lys and the chelator.

[0536] Embodiment 79. The compound of Embodiment 78, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein the chelating agent is selected from DOTA, DOTAGA, LSC, NOPO, PCTA, DOTAM, Macropa, Crown, NOTA, and NODAGA.

[0537] Embodiment 80. The compound of any one of Embodiments 78 and 79, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein a linker, if inserted, is selected from O2Oc, Pab, Ahx, APAc, Pamb, Cmp and Ttds.

[0538] Embodiment 81. A compound of any one of Embodiments 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79 and 80, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa7 is selected from Apc(DOTA), Lys(DOTAGA-O2Oc), Lys(DOTA-O2Oc), Lys(DOTA-Pab), Lys(DOTA-Ahx), Lys(DOTA-APAc), Lys(DOTA-Pamb), Lys(DOTA-Cmp), Lys(DOTA-Ttds), Lys(DOTA).

[0539] Embodiment 82. The compound of any one of Embodiments 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, and 77, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein Xaa7 is selected from Formula (X), wherein

[0540] u is 4;

[0541] L 3 Yes-(Xab1) v -;

[0542] v is 1; and

[0543] Xab1 is selected from the group consisting of Ttds, Pamb, APAc, O2Oc, Ahx and Pab.

[0544] Implementation Plan 83. Implementation Plan 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, A compound of any one of 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81 and 82, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein the chelating agent is selected from DOTA, DOTAGA, LSC, NOPO, PCTA, DOTAM, Macropa, Crown, NOTA and NODAGA.

[0545] Embodiment 84. The compound of Embodiment 83, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein the chelating agent is selected from DOTA and DOTAGA.

[0546] Embodiment 85. The compound of Embodiment 84, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein the chelating agent is DOTA.

[0547] Implementation Plan 86. Implementation Plans 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54 , 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84 and 85, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa2 is selected from Aib, Ala, Ams, ams, Deg, Pam and Pro.

[0548] Embodiment 87. The compound of Embodiment 86, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa2 is selected from Aib, Ala, Pam, Deg, Ams and ams.

[0549] Embodiment 88. The compound of Embodiment 87, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa2 is Aib.

[0550] Embodiment 89. The compound of Embodiment 87, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa2 is Ala.

[0551] Implementation Plan 90. Implementation Plan 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66 6, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88 and 89, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa3 is selected from Phe, 1Ni, 2Ni, 6Clw, Cys(Bzl), Hfe and Trp, wherein Phe, Nmf and Hfe are optionally substituted with 1 or 2 substituents independently selected from Cl, CH3, F, CN, CF3 and OH.

[0552] Embodiment 91. The compound of Embodiment 90, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein Xaa3 is selected from Phe, Nmf, and Hfe, and wherein Phe, Nmf, and Hfe are optionally substituted with one substituent selected from Cl, CH3, F, CN, CF3, and OH.

[0553] Embodiment 92. The compound of Embodiment 91, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa3 is Phe optionally substituted with one substituent selected from Cl, CH3, F, CN, CF3 and OH.

[0554] Embodiment 93. The compound of Embodiment 92, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa3 is Phe optionally substituted with one substituent selected from Cl, CH3, F, CN, CF3.

[0555] Embodiment 94. The compound of Embodiment 93, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein Xaa3 is selected from Phe, PCf, Mcf, MWf, Mnf, Mmf, Pmf, Pnf, Pff, Mtf, and Ptf.

[0556] Embodiment 95. The compound of Embodiment 94, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa3 is selected from Phe and Pcf.

[0557] Embodiment 96. The compound of Embodiment 94, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa3 is Phe.

[0558] Embodiment 97. The compound of Embodiment 94, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa3 is Pcf.

[0559] Implementation Plan 98. Implementation Plans 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59 , 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96 and 97, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa5 is selected from Formula (Va), Formula (Vb), Hgn and Nle, and

[0560] R 5g 、R 5h and R 5i It is CH3.

[0561] Embodiment 99. The compound of Embodiment 98, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein Xaa5 is selected from Formula (Va), and

[0562] R 5a Selected from H, CH3, Ac and C(=NR 5d )NR 5e R 5f ;

[0563] R 5e and R 5f independently selected from H and CH3;

[0564] R 5b is H;

[0565] R 5c is H; and

[0566] m is selected from 3 and 4.

[0567] Embodiment 100. The compound of embodiment 99 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein R 5a is selected from H and CH3; and m is 4.

[0568] Embodiment 101. The compound of any one of Embodiments 98, 99 and 100, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa5 is Lys.

[0569] Embodiment 102. The compound of any one of Embodiments 98, 99 and 100, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa5 is Lys(Me).

[0570] Embodiment 103. The compound of any one of Embodiments 98, 99 and 100, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa5 is Kip.

[0571] Embodiment 104. The compound of any one of Embodiments 98, 99 and 100, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa5 is KMe3.

[0572] Implementation Plan 105. Implementation Plans 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103 and 104, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa6 is selected from Formula (VI), Formula (VII) and Nle,

[0573] where R 6a Selected from H, C(=NR 6e )NR 6f R 6g and C(=O)R 6h ;

[0574] R6e is H;

[0575] R 6f Selected from H, CH3, Ac, NO2 and C(=O)NR 6i R 6j ;

[0576] R 6g selected from H and CH3;

[0577] R 6h selected from CH3, NH2 and NHC(=NH)NH2;

[0578] R 6b is H;

[0579] R 6c is H; and

[0580] R 6d Selected from NHC(=NH)NH2 and NH2.

[0581] Embodiment 106. The compound of Embodiment 105, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein Xaa6 is selected from Arg, Arg(Me), Cit, Egd, RMe2a, RMe3, Nle, Gln, Lys(Ac), Hgn, Arg(EtCAyl), Urr, Arg(Ac), Gln(Gu), Orn, Har, RMe2, and Eew.

[0582] Embodiment 107. The compound of embodiment 105, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa6 is selected from formula (VI), and wherein

[0583] n is 3;

[0584] R 6a is C(=NH)NHR 6f ;as well as

[0585] R 6f Selected from H, Ac, NO2 and CH3.

[0586] Embodiment 108. The compound of any one of Embodiments 105, 106 and 107, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa6 is Arg.

[0587] Embodiment 109. The compound of any one of Embodiments 105, 106 and 107, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa6 is Arg(Me).

[0588] Embodiment 110. The compound of any one of Embodiments 105 and 106, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa6 is Cit.

[0589] Embodiment 111. The compound of any one of Embodiments 105 and 106, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa6 is Egd.

[0590] Embodiment 112. The compound of any one of Embodiments 105 and 106, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa6 is RMe2a.

[0591] Embodiment 113. The compound of any one of Embodiments 105 and 106, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa6 is RMe3.

[0592] Implementation Plan 114. Implementation Plans 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70 , 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112 and 113, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa8 is selected from Formula (XIV), Gly, Val, Met, Ile and Thr:

[0593]

[0594] where R 8a is selected from H, OH, NH2, COOH, C(=O)NH2, NHC(=NH)NH2, (C1-C8)alkyl, aryl and heteroaryl;

[0595] w is selected from 1, 2, and 3; and

[0596] R 8bSelected from H and CH3.

[0597] Embodiment 115. The compound of embodiment 114 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein

[0598] R 8a selected from OH, COOH, C(=O)NH2, phenyl, NHC(=NH)NH2, indole, and CH(CH3)2; and

[0599] w is selected from 1 and 2.

[0600] Embodiment 116. The compound of any one of Embodiments 114 and 115, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein Xaa8 is selected from Asn, Trp, Phe, Arg, Ser, Gly, Leu, Asp, Nmn, Glu, and Asn.

[0601] Embodiment 117. The compound of Embodiment 116, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa8 is Asn.

[0602] Implementation Plan 118. Implementation Plan 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, and 117, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein Xaa10 is Formula (XII):

[0603] in

[0604] R 10b selected from H and CH3;

[0605] R 10c It’s H.

[0606] Embodiment 119. The compound of Embodiment 118, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa10 is selected from Tle, Leu, Val, Npg and Ile.

[0607] Embodiment 120. The compound of Embodiment 119, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa10 is selected from Tle, Leu, Val and Npg.

[0608] Embodiment 121. The compound of Embodiment 120, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa10 is Tle.

[0609] Embodiment 122. The compound of Embodiment 120, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa10 is Leu.

[0610] Embodiment 123. A compound of any one of Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, and 33, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein the compound is of Formula (Ia).

[0611]

[0612] Embodiment 124. The compound of Embodiment 123, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein Xaa3 is selected from Phe, 1Ni, 2Ni, 6Clw, Cys(Bzl), Hfe, and Trp, wherein Phe, Nmf, and Hfe are optionally substituted with 1 or 2 substituents independently selected from Cl, CH3, F, CN, CF3, and OH.

[0613] Embodiment 125. The compound of Embodiment 124, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein Xaa3 is selected from Phe, Nmf, and Hfe, and wherein Phe, Nmf, and Hfe are optionally substituted with one substituent selected from Cl, CH3, F, CN, CF3, and OH.

[0614] Embodiment 126. The compound of Embodiment 125, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa3 is Phe optionally substituted with one substituent selected from Cl, CH3, F, CN, CF3 and OH.

[0615] Embodiment 127. The compound of Embodiment 125, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa3 is Phe.

[0616] Embodiment 128. The compound of Embodiment 125, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa3 is Pcf.

[0617] Embodiment 129. The compound of any one of Embodiments 123, 124, 125, 126, 127 and 128, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa10 is of formula (XII), wherein

[0618]

[0619] R 10b selected from H and CH3;

[0620] R 10c It’s H.

[0621] Embodiment 130. The compound of embodiment 129 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa10 is selected from a compound of formula (XIV)

[0622]

[0623] Embodiment 131. The compound of any one of Embodiments 129 and 130, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein R 10a Selected from C(CH3)3, CH2CH(CH3)2, CH(CH3)2, CH(CH3)2, CH(CH3)C2H5 and CH2C(CH3)3.

[0624] Embodiment 132. The compound of embodiment 131 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein R 10a It is C(CH3)3.

[0625] Embodiment 133. The compound of embodiment 131 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein R 10a It is CH2CH(CH3)2.

[0626] Embodiment 134. The compound of any one of Embodiments 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, and 133, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein the compound is a compound of formula (Ib)

[0627]

[0628] where R 3c selected from H, Cl, CH3, F, CN, CF3 and OH; and

[0629] R 3c At the meta-position or para-position of the benzene ring of formula (Ib).

[0630] Embodiment 135. The compound of embodiment 134, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein R 3c For H.

[0631] Embodiment 136. The compound of embodiment 134, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein R 3c is Cl, where R 3c It is located in the para position of the benzene ring of formula (Ib).

[0632] Embodiment 137. The compound of any one of Embodiments 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133 and 134, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein

[0633] R 5a selected from H, CH3, C(CH3)2, Ac and C(=NR 5d )NR 5e R 5f ;

[0634] R 5d 、R 5e and R 5f independently selected from H and CH3;

[0635] R 5b selected from H and CH3; and

[0636] m is selected from 3 and 4.

[0637] Embodiment 138. The compound of embodiment 137 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein R 5a Selected from H and CH3, R 5b is H and m is 4.

[0638] Example 139. The compound of embodiment 137, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein R 5a CH3, R 5b is H and m is 4.

[0639] Embodiment 140. The compound of embodiment 137, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein R 5a C(CH3)2, R 5b is H and m is 4.

[0640] Embodiment 141. A compound of any one of Embodiments 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, and 140, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein

[0641] R 6a Selected from H, C(=NR 6e )NR 6f R 6g and C(=O)R 6h ;

[0642] R 6e selected from H and CH3,

[0643] R 6f Selected from H, CH3, Ac, NO2 and C(=O)NR 6i R 6j ;

[0644] R 6i selected from H and (C1-C2)alkyl;

[0645] R 6j is H;

[0646] R 6g selected from H and CH3;

[0647] R 6h selected from CH3, NH2 and NHC(=NH)NH2;

[0648] R 6b and R 6c are each independently selected from H and CH3; and

[0649] n is selected from 3 and 4.

[0650] Embodiment 142. The compound of embodiment 141, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein n is selected from 3 and 4, and R 6c For H.

[0651] Embodiment 143. A compound of any one of Embodiments 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, and 142, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein

[0652] n is 3; and

[0653] R 6a is C(=NR 6e )NR 6f R 6g ;

[0654] R 6e is H;

[0655] R 6f Selected from H, CH3, Ac, NO2 and C(=O)NHR 6i ;

[0656] R 6g is H; and

[0657] R 6b It’s H.

[0658] Embodiment 144. The compound of embodiment 143, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein R 6f Selected from H, Ac, NO2 and CH3.

[0659] Embodiment 145. The compound of any one of Embodiments 141, 142, 143 and 144, preferably the compound of Embodiment 143, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein R 6f For H.

[0660] Embodiment 146. The compound of any one of Embodiments 141, 142, 143 and 144, preferably the compound of Embodiment 143, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein R 6f For CH3.

[0661] Embodiment 147. The compound of any one of Embodiment 143, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein

[0662] n is 3, and R 6e 、R 6f and R 6g are each independently selected from CH3.

[0663] Embodiment 148. The compound of any one of Embodiments 141 and 142, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein

[0664] n is 3; and

[0665] R 6a is C(=O)R 6h , where R 6h It's NH2.

[0666] Embodiment 149. The compound of any one of Embodiments 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, and 148, wherein

[0667] R 7a is selected from H, (C1-C2)alkyl, CH2OH and CH2CO2H and CH2CH2CO2H; and

[0668] R 7b is selected from H and (C1-C2)alkyl.

[0669] Embodiment 150. The compound of embodiment 149 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein R 7c For H.

[0670] Embodiment 151. The compound of any one of Embodiments 149 and 150, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein

[0671] R 7a selected from (C1-C2)alkyl, CH2OH, CH2CO2H and CH2CH2CO2H; and

[0672] R 7b Selected from (C1-C2)alkyl.

[0673] Embodiment 152. The compound of embodiment 151, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein R 7a is CH3; and R 7b For CH3.

[0674] Embodiment 153. The compound of embodiment 151, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein R 7a is H; and R 7b It is CH3.

[0675] Embodiment 154. A compound of any one of Embodiments 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, and 153, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein

[0676] R 8a is selected from H, OH, COOH, C(═O)NH2, CH2CH2NHC(═NH)NH2, (C1-C8)alkyl, aryl and heteroaryl;

[0677] R 8b Selected from H and CH3.

[0678] Embodiment 155. A compound of any one of Embodiments 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, and 154, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein

[0679] R 8a Selected from OH, COOH, C(=O)NH2, CH(CH3)2, CH2CH2NHC(=NH)NH2, phenyl and indole.

[0680] Embodiment 156. The compound of embodiment 155, wherein R 8b It’s H.

[0681] Embodiment 157. The compound of any one of Embodiments 154, 155 and 156, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein R 8a It is C(=O)NH2.

[0682] Embodiment 158. The compound of any one of Embodiments 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, and 157, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein R 3c Selected from H, Cl, CH3, F, CN and CF3.

[0683] Embodiment 159. The compound of embodiment 158, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein R 3c For H.

[0684] Embodiment 160. The compound of embodiment 158, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein R 3c It is Cl and is in the para position.

[0685] Embodiment Example 161. A compound of any one of Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, and 33, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or hydrate thereof, wherein

[0686] Xaa2 is Aib or Ala;

[0687] Xaa3 is Phe or PCf;

[0688] Xaa5 is Lys(Me), Lys, Kip, or KMe3;

[0689] Xaa6 is Arg(Me), Arg, Egd, Cit, RMe2a, or RMe3;

[0690] Xaa7 is Aib or Ala;

[0691] Xaa8 is Asn; and

[0692] Xaa10 is Tle or Leu.

[0693] Embodiment 162. The compound of embodiment 161 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein

[0694] Xaa2 is Aib or Ala;

[0695] Xaa3 is Phe or PCf;

[0696] Xaa5 is Lys(Me), Lys, or Kip;

[0697] Xaa6 is Arg(Me), Arg, Egd, Cit, or RMe2a;

[0698] Xaa7 is Aib or Ala;

[0699] Xaa8 is Asn; and

[0700] Xaa10 is Tle or Leu.

[0701] Embodiment 163. The compound of embodiment 161 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein

[0702] Xaa2 is Aib or Ala;

[0703] Xaa3 is Phe or PCf;

[0704] Xaa5 is Lys(Me) or Lys;

[0705] Xaa6 is Arg(Me) or Arg;

[0706] Xaa7 is Aib or Ala;

[0707] Xaa8 is Asn; and

[0708] Xaa10 is Tle or Leu.

[0709] Embodiment 164. The compound of embodiment 161 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein

[0710] Xaa2 is Aib or Ala;

[0711] Xaa3 is Phe or PCf;

[0712] Xaa5 is Lys(Me) or Lys;

[0713] Xaa6 is Arg(Me) or Arg;

[0714] Xaa7 is Aib or Ala;

[0715] Xaa8 is Asn; and

[0716] Xaa10 is Tle.

[0717] Embodiment 165. The compound of any one of Embodiments 161, 162, 163, 164 and 165, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein

[0718] Z 1 is a chelating agent; and

[0719] L 1 Formula (XIII)

[0720] -Xaa1 b -Xaa1 a -,

[0721] (XIII)

[0722] Among them, Xaa1 a Covalently bound to Xaa2;

[0723] Xaa1 a is Thr; and

[0724] Xaa1 b It's Cmp.

[0725] Embodiment 166. The compound of any one of Embodiments 161, 162, 163 and 164, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein

[0726] Z 1 is a chelating agent; and

[0727] L 1 For Pamb.

[0728] Embodiment 167. The compound of any one of Embodiments 161, 162, 163, 164, 165 and 166, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein

[0729] Z 2 is NH2; and

[0730] L 2 For Thr.

[0731] Embodiment 168. The compound of any one of Embodiments 161, 162, 163, 164, 165 and 166, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein

[0732] Z 2 is NH2; and

[0733] L 2 It's Bal.

[0734] Embodiment 169. The compound of any one of Embodiments 161, 162, 163, 164, 165 and 166, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein

[0735] Z 2 is NH2; and

[0736] L 2 It is Thr-Asp.

[0737] Embodiment 170. The compound of any one of Embodiments 161, 162, 163, 164, 165 and 166, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein

[0738] Z 2 is NH2; and

[0739] L 2 It is a key.

[0740] Embodiment 171. A compound of any one of Embodiments 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, and 66, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein

[0741] Xaa2 is Aib or Ala;

[0742] Xaa3 is Phe or PCf;

[0743] Xaa5 is Lys or Lys(Me);

[0744] Xaa6 is Arg or Arg(Me);

[0745] Xaa7 is Aib or Ala;

[0746] Xaa8 is Ans; and

[0747] Xaa10 is Tle or Leu.

[0748] Embodiment 172. The compound of embodiment 171 or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein

[0749] Z 1 is Ac; and

[0750] L 1 For Thr.

[0751] Embodiment 173. The compound of embodiment 171 or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein

[0752] Z 1 is Ac; and

[0753] L 1 It is a key.

[0754] Embodiment 174. The compound of embodiment 171 or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein

[0755] Z 1 is Ac; and

[0756] L 1 Formula (XIII)

[0757] -Xaa1 b -Xaa1 a -,

[0758] (XIII)

[0759] Among them, Xaa1 a covalently bound to Xaa2 of formula (I);

[0760] Xaa1 a is Thr; and

[0761] Xaa1 b It is Met or Cmp.

[0762] Embodiment 175. The compound of any one of Embodiments 171, 172, 173 and 174, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein

[0763] Z2 is a chelating agent; and

[0764] L2 is en.

[0765] Embodiment 176. The compound of any one of Embodiments 171, 172, 173 and 174, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein

[0766] Z2 is a chelating agent; and

[0767] L2 is -Xaa11-Xaa12 a -Xaa12 b -;in

[0768] Xaa11 is Thr;

[0769] Xaa12 a is Asp; and

[0770] Xaa12 b It’s Ttds.

[0771] Embodiment 177. The compound of any one of Embodiments 171, 172, 173 and 174, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein

[0772] Z2 is a chelating agent; and

[0773] L2 is -Xaa11-Xaa12;

[0774] Xaa11 is Thr;

[0775] Xaa12 a is Cmp; and

[0776] Xaa12 b It’s Ttds.

[0777] Implementation Plan 178. Implementation Plans 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 16 0, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176 and 177, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the chelating agent is selected from DOTA, DOTAGA, LSC, NOPO, PCTA, DOTAM, Macropa, Crown, NOTA and NODAGA.

[0778] Embodiment 179. The compound of Embodiment 178, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the chelating agent is selected from DOTA and DOTAGA.

[0779] Embodiment 180. The compound of Embodiment 179, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the chelating agent is DOTA.

[0780] Embodiment 181. The compound of Embodiment 1 or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the compound is selected from the following compounds:

[0781] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0194);

[0782] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-NH2(PSM-0433);

[0783] DOTA-Cmp-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0492);

[0784] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0178);

[0785] Ac-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0179);

[0786] Ac-Thr-Aib-Phe-[Cys-Lys-Gln-Ala-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0180);

[0787] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Hyp-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0l81);

[0788] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-Ttds-Ttds-AF488N3K-NH2(PSM-0183);

[0789] DOTA-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-NH2(PSM-0184);

[0790] Ac-Pamp-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en-DOTA(PSM-0186);

[0791] Ac-Thr-Deg-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0187);

[0792] SaPr-Aib-Pcf-[Cys-Lys-Arg-Lys(DOTA-APAc)-Asn-Cys]-Tle-Thr-NH2(PSM-0188);

[0793] Ac-Thr-Aib-Pcf-[Cys-Lys-Gln(Gu)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0189);

[0794] Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-lys(DOTA-Cmp)-NH2(PSM-0190);

[0795] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-APAc-lys(DOTA)-NH2(PSM-0191);

[0796] DOTA-Ttds-Thr-Aib-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0193);

[0797] Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Glu-Asn-Cys]-Nle-Thr-Asp-NH2(PSM-0197);

[0798] DOTA-Cmp-Tle-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0198);

[0799] DOTA-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en(PSM-0199);

[0800] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg-Aib-Asn-Cys]-Tle-NH2(PSM-0200);

[0801] DOTA-Pamb-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0202);

[0802] DOTA-Cmp-Thr-Aib-Pcf-[Cys-KMe2-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0203);

[0803] nBuCAyl-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0204);

[0804] Ac-Thr-Aib-Pcf-[Cys-Nle-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0205);

[0805] nBuCAyl-Thr-Aib-Mcf-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0207);

[0806] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-NHnPen(PSM-0208);

[0807] DOTA-Bal-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0209);

[0808] Ac-Thr-Aib-Phe-[Cys-Gln-Arg-Aib-Asr-Cys]-Tle-Thr-Asp-NH2(PSM-0210);

[0809] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Lys(DOTA-Pab)-Asn-Cys]-Tle-Thr-NH2(PSM-0211);

[0810] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-Ttds-lys(DOTA)-NH2(PSM-0212);

[0811] SaPr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0215);

[0812] DOTA-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Bal-NH2(PSM-0216);

[0813] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Dfp-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0217);

[0814] DOTAGA-Cmp-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0218);

[0815] DOTA-Cmp-Leu-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0220);

[0816] DOTA-Pamb-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en(PSM-0221);

[0817] DOTA-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en(PSM-0222);

[0818] DOTA-Cmp-Aib-Pcf-[Cys-Lys-Arg(Ac)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0223);

[0819] SaPr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0224);

[0820] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Har-Arg-Aib-Asn-Cysr-Tle-Thr-NH2(PSM-0225);

[0821] H-Met-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Leu-Thr-Asp-Gly-Ser-Ttds-Ttds-Ttds-

[0822] Lys(Bio)-NH2(PSM-0226);

[0823] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-amd-Asn-Cys]-Tle-Thr-NH2(PSM-0227);

[0824] Ac-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0228);

[0825] Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Met-Cys]-Tle-Thr-NH2(PSM-0229);

[0826] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-NH2(PSM-0230);

[0827] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-Ttds-lys(DOTA)-NH2(PSM-0231);

[0828] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Nmg-Asn-Cys]-Tle-Thr-NH2(PSM-0232);

[0829] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Pam-Asn-Cys]-Tle-Thr-NH2(PSM-0233);

[0830] DOTA-Ttds-Thr-Aib-Phe-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0234);

[0831] Ac-Thr-Aib-Phe-[Cys-Lys-Nmr-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0235);

[0832] Ac-Thr-Aib-Pcf-[Cys-Nle-Gln(Gu)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0236);

[0833] DOTA-Ttds-Thr-Aib-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-NH2(PSM-0237);

[0834] Ac-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Trp-Cys]-Tle-Thr-NH2(PSM-0238);

[0835] Hex-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-lys(DOTA-Cmp)-NH2(PSM-0239);

[0836] Ac-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Arg-Cys]-Tle-Thr-NH2(PSM-0240);

[0837] DOTA-Cmp-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en(PSM-0241);

[0838] Ac-Thr-Aib-Mcf-[Cys-Lys-Arg-Lys(DOTA-O2Oc)-Asn-Cys]-Tle-Thr-NH2(PSM-0243);

[0839] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Kip-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0244);

[0840] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Orn-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0245);

[0841] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-ala-Asn-Cys]-Tle-Thr-NH2(PSM-0246);

[0842] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-RMe2-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0247);

[0843] DOTA-Cmp-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0248);

[0844] Ac-Thr-Aib-1Ni-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0249);

[0845] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Ttds-Ttds-Lys(Bio)-NH2(PSM-0250);

[0846] DOTA-Ttds-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Leu-Thr-Asp-NH2(PSM-0251);

[0847] Ac-Thr-Aib-Phe-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0252);

[0848] Ac-Thr-Aib-Phe-[Cys-Lys-Glu-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0253);

[0849] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Eew-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0254);

[0850] DOTA-Cmp-Thr-Aib-Mpa-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0255);

[0851] DOTA-Cmp-Thr-ams-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0256);

[0852] DOTA-Cmp-Thr-Aib-Opa-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0257);

[0853] nBuCAyl-Thr-Aib-Phe-[Cys-Lys-Opy-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0258);

[0854] DOTA-Ttds-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0259);

[0855] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-glu-Asn-Cys]-Tle-Thr-NH2(PSM-0260);

[0856] DOTA-APAc-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0261);

[0857] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Glu-NH2(PSM-0262);

[0858] DOTA-APAc-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0263);

[0859] Ac-Thr-Aib-Mtf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0264);

[0860] Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-Ttds-lys(DOTA)-NH2(PSM-0266);

[0861] HPA-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-lys(DOTA)-NH2(PSM-0267);

[0862] Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en-DOTA(PSM-0269);

[0863] DOTA-Pamb-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0270);

[0864] AF488Ahx-Ttds-Ttds-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0272);

[0865] DOTA-Pamb-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en(PSM-0273);

[0866] DOTA-Cmp-Thr-Aib-Eaa-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0274);

[0867] Ac-Thr-Aib-Mcf-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0275);

[0868] Ac-Thr-Aib-Pnf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0278);

[0869] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Ser-Cys]-Tle-Thr-NH2(PSM-0279);

[0870] Ac-Thr-Aib-Phe-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0280);

[0871] Ac-Aib-Pcf-[Cys-Lys-Arg-Lys(DOTA-APAc)-Asn-Cys]-Tle-Thr-NH2(PSM-0282);

[0872] DOTA-Pamb-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0283);

[0873] Ac-Thr-Aib-Mcf-[Cys-Lys-Cit-Lys(DOTA-O2Oc)-Asn-Cys]-Tle-Thr-NH2(PSM-0284);

[0874] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Trds-lys(DOTA)-NH2(PSM-0285);

[0875] Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Thr-Asp-NH2(PSM-0287);

[0876] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-lys(DOTA)-NH2(PSM-0288);

[0877] Hex-Thr-Aib-Phe-[Cys-Lys-Gln-Aib-Asn-Cys]-Tle-Thr-Ttds-lys(DOTA)-NH2(PSM-0289);

[0878] Iva-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-lys(DOTA)-NH2(PSM-0292);

[0879] Ac-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Ser-Cys]-Tle-Thr-NH2(PSM-0293);

[0880] Ac-Thr-Aib-Pff-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0294);

[0881] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-Ttds-lys(DOTA)-NH2(PSM-0295);

[0882] DOTA-Cmp-Thr-Aib-Mpa-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0296);

[0883] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Gab-NH2(PSM-0297);

[0884] Ac-Aib-Pcf-[Cys-Lys-Arg(Ac)-Aib-Asn-Cys]-Tle-Thr-Cmp-]ys(DOTA)-NH2(PSM-0298);

[0885] Ac-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Leu-Thr-Asp-Ttds-lys(DOTA)-NH2(PSM-0299);

[0886] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-OH(PSM-0300);

[0887] Ac-Thr-Aib-Mcf-[Cys-Lys-Arg-Lys(DOTAGA-O2Oc)-Asn-Cys]-Tle-Thr-NH2(PSM-0301);

[0888] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Amd-Asn-Cys]-Tle-Thr-NH2(PSM-0302);

[0889] Ac-Thr-Aib-Phe-[Cys-Lys-Gln-Aib-Asn-Cys]-Tle-Thr-Ttds-lys(DOTA)-NH2(PSM-0303);

[0890] DOTA-Cmp-Thr-Aib-6Clw-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0304);

[0891] DOTA-Ttds-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Leu-Thr-NH2(PSM-0305);

[0892] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en(Me)2(PSM-0306);

[0893] Ac-Thr-Aib-Phe-[Cys-Lys-Cit-Ala-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0307);

[0894] DOTA-Cmp-Thr-Aib-5Clw-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0308);

[0895] DOTA-Ahx-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-03l0);

[0896] Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Thr-Gab-OH(PSM-0313);

[0897] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-ams-Asn-Cys]-Tle-Thr-NH2(PSM-0314);

[0898] Ac-Thr-Aib-Phe-[Cys-Lys-arg-Ala-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0315);

[0899] DOTA-Pab-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0316);

[0900] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Har-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0317);

[0901] Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0318);

[0902] Ac-Thr-Ala-Nmf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0319);

[0903] Ac-Aib-Pcf-[Cys-Lys-Arg(Me)-Aib-Asn-Cys]-Tle-en-DOTA (PSM-0320);

[0904] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Apc(DOTA)-Asn-Cys]-Tle-Thr-NH2 (PSM-0321);

[0905] Ac-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-lys(DOTA-Cmp)-NH2 (PSM-0322);

[0906] HPA-Aib-Pcf-[Cys-Lys-Arg-Lys(DOTA-APAc)-Asn-Cys]-Tle-Thr-NH2 (PSM-0324);

[0907] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Lys(DOTA)-Asn-Cys]-Tle-Thr-NH2 (PSM-0326);

[0908] SaPr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-lys(DOTA)-NH2 (PSM-0328);

[0909] Ac-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2 (PSM-0329);

[0910] Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Leu-Thr-Asp-Ttds-lys(DOTA)-NH2 (PSM-0330);

[0911] DOTA-Cmp-Thr-Aib-Pcf-[Smc-Lys-Arg-Aib-Asn-Cys]-Tle-NH2 (or: DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Smc]-Tle-NH2) (PSM-0332);

[0912] Ac-Thr-Aib-Phe-[Cys-Lys-Gln-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0334);

[0913] Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Ala-Cys]-Nle-Thr-Asp-NH2(PSM-0335);

[0914] Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0336);

[0915] Ac-Thr-Aib-Pcf-[Cys-Lys-Nle-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0338);

[0916] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTAGA)-NH2(PSM-0339);

[0917] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Nmr-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0340);

[0918] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Lys(Ac)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0341);

[0919] DOTA-Ttds-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0342);

[0920] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg(Me)-Aib-Asn-Cys]-Tle-NH2(PSM-0345);

[0921] DOTA-Cmp-Thr-Amd-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0346);

[0922] Ac-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0349);

[0923] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-leu-Thr-NH2(PSM-0350);

[0924] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0351);

[0925] DOTA-Bal-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0352);

[0926] Iva-Aib-Pcf-[Cys-Lys-Arg-Lys(DOTA-APAc)-Asn-Cys]-Tle-Thr-NH2(PSM-0353);

[0927] DOTA-Cmp-Thr-Aib-Mcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-NH2(PSM-0354);

[0928] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-RMe3-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0355);

[0929] DOTA-Cmp-Ile-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0357);

[0930] DOTA-Cmp-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-NH2(PSM-0361);

[0931] Ac-Thr-Aib-Phe-[Cys-Lys-Glu-Ala-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0363);

[0932] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0365);

[0933] DOTA-Cmp-Thr-amd-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0366);

[0934] Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-NH2(PSM-0367);

[0935] DOTA-Ahx-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0368);

[0936] DOTA-Cmp-Thr-Ams-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0369);

[0937] Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Lys(DOTA-O2Oc)-Asn-Cys]-Tle-Thr-NH2(PSM-0370);

[0938] nBuCAyl-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0371);

[0939] Ac-Thr-Aib-Pmf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0372);

[0940] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0374);

[0941] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Deg-Asn-Cys]-Tle-Thr-NH2(PSM-0375);

[0942] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Trp-NH2(PSM-0376);

[0943] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Val-Nmt-NH2(PSM-0377);

[0944] H-Cmp-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0378);

[0945] Ac-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en-DOTA(PSM-0379);

[0946] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-NH2(PSM-0380);

[0947] DOTA-Pamb-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-NH2(PSM-0381);

[0948] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Ams-Asn-Cys]-Tle-Thr-NH2(PSM-0382);

[0949] Ac-Thr-Aib-Mcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0383);

[0950] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en(PSM-0384);

[0951] Ac-Thr-Aib-Phe-[Cys-Lys-Gln-Lys(DOTA)-Asn-Cys]-Tle-Thr-NH2(PSM-0385);

[0952] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Pro-NH2(PSM-0388);

[0953] Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Thr-asP-NH2(PSM-0389);

[0954] DOTA-Cmp-Thr-Aib-6Clw-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-NH2(PSM-0390);

[0955] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Ape-DOTA(PSM-0391);

[0956] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-4Tfp-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0392);

[0957] Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en(PSM-0393);

[0958] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Aib-Thr-NH2(PSM-0394);

[0959] DOTA-Cmp-Thr-Aib-Pff-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-NH2(PSM-0395);

[0960] DOTA-Cmp-Thr-Aib-Mtf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-NH2(PSM-0396);

[0961] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Lys(DOTA)-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0397);

[0962] DOTA-Ttds-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0398);

[0963] Hex-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-lys(DOTA-Cmp)-NH2(PSM-0400);

[0964] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Lys(DOTA-O2Oc)-Asn-Cys]-Tle-Thr-NH2(PSM-0401);

[0965] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-asn-Cys]-Tle-Thr-NH2(PSM-0402);

[0966] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Oic-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0403);

[0967] Ac-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-lys(DOTA)-NH2(PSM-0404);

[0968] Hex-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Leu-Thr-Asp-Ttds-lys(DOTA)-NH2(PSM-0405);

[0969] DOTA-Cmp-Thr-Ams-Pcr-[Cys-Lys-Arg-Ams-Asn-Cys]-Tle-Thr-NH2(PSM-0407);

[0970] Ac-Thr-Nmg-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0408);

[0971] DOTA-Cmp-Thr-Aib-Opa-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-NH2(PSM-0409);

[0972] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0410);

[0973] Ac-Thr-Aib-Hfe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0411);

[0974] Ac-Thr-Aib-Mmf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0412);

[0975] DOTA-PPAc-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0413);

[0976] Ac-Thr-Ala-Amf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0414);

[0977] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Lys(DOTA-Cmp)-Asn-Cys]-Tle-Thr-NH2 (PSM-0415);

[0978] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Glu-Asn-Cys]-Tle-Thr-NH2 (PSM-0416);

[0979] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Lys(DOTA-Pamb)-Asn-Cys]-Tle-Thr-NH2 (PSM-0419);

[0980] DOTA-Cmp-Thr-Aib-Pcf-[Smc-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-NH2 (or: DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Smc]-Tle-NH2) (PSM-0420);

[0981] Ac-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Asn-Cys]-leu-Thr-NH2 (PSM-0421);

[0982] Ac-Thr-Aib-Phe-[Cys-Tap-Arg-Ala-Asn-Cys]-Tle-Thr-AsP-NH2(PSM-0422);

[0983] Ac-Thr-Aib-Phe-[Cys-Lys-Gln-Lys(DOTA-Ttds)-Asn-Cys]-Tle-Thr-NH2(PSM-0423);

[0984] Ac-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-NH2(PSM-0424);

[0985] Hex-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-Ttds-lys(DOTA)-NH2(PSM-0425);

[0986] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Bal-NH2(PSM-0426);

[0987] nBuCAyl-Thr-Aib-Pcf-[Cys-Lys-Opy-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0427);

[0988] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0428);

[0989] DOTA-Cmp-Thr-Aib-Mcf-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0431);

[0990] DOTA-Pamb-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Bal-NH2(PSM-0432);

[0991] nBuCAyl-Thr-Aib-Phe-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0434);

[0992] Ac-Thr-Aib-Phe-[Cys-Gln-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0435);

[0993] DOTA-Bal-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0437);

[0994] Ac-Thr-Aib-Phe-[Cys-Aph-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0439);

[0995] Ac-Thr-Aib-Cys(Bzl)-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0441);

[0996] Ac-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0442);

[0997] Ac-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-NH2(PSM-0443);

[0998] Iva-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-lys(DOTA)-NH2(PSM-0444);

[0999] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0445);

[1000] DOTA-Pab-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0448);

[1001] DOTA-Cmp-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Bal-NH2(PSM-0449);

[1002] Iva-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0450);

[1003] Ac-Thr-Aib-Phe-[Cys-Nmk-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0451);

[1004] nBuCAyl-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-lys(DOTA-Cmp)-NH2(PSM-0452);

[1005] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Leu-NH2(PSM-0453);

[1006] DOTA-Cmp-Thr-Aib-Ppa-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0454);

[1007] DOTA-Cmp-Nmt-Ala-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0455);

[1008] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en(Me)(PSM-0456);

[1009] DOTA-Pamb-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-NH2(PSM-0458);

[1010] DOTA-Cmp-Thr-Aib-Mnf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-NH2(PSM-0459);

[1011] Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Pro-Asn-Cys]-Nle-Thr-Asp-NH2(PSM-0460);

[1012] Hib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0461);

[1013] Hex-Thr-Aib-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-Ttds-lys(DOTA)-NH2(PSM-0462);

[1014] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Lys(DOTA-APAc)-Asn-Cys]-Tle-Thr-NH2(PSM-0464);

[1015] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Lys(DOTA-Ttds)-Asn-Cys]-Tle-Thr-NH2(PSM-0465);

[1016] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Ac)-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0466);

[1017] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Bal-NH2(PSM-0467);

[1018] Ac-Ser-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Thr-Asp-NH2(PSM-0469);

[1019] nBuCAyl-Thr-Aib-Mcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0470);

[1020] Ac-Tbr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Pab-lys(DOTA)-NH2(PSM-0471);

[1021] Ac-Aib-Pcf-[Cys-Lys(Me)-Arg-Aib-Asn-Cys]-Tle-en-DOTA(PSM-0472);

[1022] Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Ala-Asp-NH2(PSM-0476);

[1023] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Gly-NH2(PSM-0477);

[1024] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asp-Cys]-Tle-Thr-NH2(PSM-0478);

[1025] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Gly-Cys]-Tle-Thr-NH2(PSM-0479);

[1026] DOTA-Ttds-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Leu-NH2(PSM-0480);

[1027] Ac-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-en-DOTA(PSM-0481);

[1028] Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0482);

[1029] DOTA-Cmp-Thr-Aib-Pcf-[Cys-KMe3-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0483);

[1030] nBuCAyl-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0484);

[1031] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Hgn-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0485);

[1032] Ac-Thr-Aib-Mcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0486);

[1033] Ac-Thr-Aib-Tyr-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0488);

[1034] DOTA-Cmp-Aib-Pcf-[Cys-Lys-Gln(Gu)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0489);

[1035] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Bio)-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0490);

[1036] Ac-Ala-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Thr-Asp-NH2(PSM-0491);

[1037] Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-OH(PSM-0493);

[1038] Ac-Aib-Pcf-[Cys-Lys-Gln(Gu)-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0494);

[1039] Crown-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0495);

[1040] Ac-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Glu-Cys]-Tle-Thr-NH2(PSM-0496);

[1041] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Nml-Thr-NH2(PSM-0497);

[1042] H-Met-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Leu-Thr-Asp-Gly-Ser-NH2(PSM-0498);

[1043] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Egd-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0499);

[1044] nBuCAyl-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-lys(DOTA-Cmp)-NH2 (PSM-0500);

[1045] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Thr-Asp-NH2 (PSM-0501);

[1046] Hex-Thr-Aib-Phe-[Cys-Lys-Aib-Ala-Asn-Cys]-Tle-Thr-Asp-Ttds-lys(DOTA)-NH2 (PSM-0502);

[1047] DOTA-Cmp-Thr-Aib-Mmf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-NH2 (PSM-0503);

[1048] DOTA-Ttds-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Thr-Asp-NH2 (PSM-0504);

[1049] DOTA-O2Oc-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0505);

[1050] Ac-Aib-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-NH2 (PSM-0506);

[1051] DOTA-Cmp-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0507);

[1052] Ac-Thr-Pam-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0508);

[1053] HPA-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0509);

[1054] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-NHBu(PSM-0510);

[1055] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Orn-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0511);

[1056] DOTA-Cmp-Thr-Aib-Opa-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0512);

[1057] DOTA-Ahx-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0513);

[1058] Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Bal-NH2(PSM-0514);

[1059] Macropa-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0515);

[1060] Ac-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en-DOTA(PSM-0516);

[1061] Ac-Thr-Aib-2Ni-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0517);

[1062] HYDAc-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0518);

[1063] DOTA-Ttds-Thr-Aib-Phe-[Cys-Lys-Gln-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0521);

[1064] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Pamb-lys(DOTA)-NH2(PSM-0522);

[1065] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-O2Oc-lys(DOTA)-NH2(PSM-0529);

[1066] HPA-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0530);

[1067] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Hgn-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0531);

[1068] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Dtc-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0532);

[1069] Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Thr-Asp-Ttds-lys(DOTA)-NH2(PSM-0533);

[1070] DOTA-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-NH2(PSM-0534);

[1071] Ac-Thr-Aib-Phe-[Cys-lys-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0535);

[1072] DOTA-Cmp-Tle-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0538);

[1073] DOTA-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Bal-NH2(PSM-0539);

[1074] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Gln-NH2(PSM-0540);

[1075] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Phe-Cys]-Tle-Thr-NH2(PSM-0541);

[1076] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Lys(DOTA-Ttds)-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0542);

[1077] DOTA-APAc-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0543);

[1078] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Leu-Cys]-Tle-Thr-NH2(PSM-0545);

[1079] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Urr-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0546);

[1080] Ac-Thr-Pro-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Thr-Asp-NH2(PSM-0547);

[1081] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Nmk-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0548);

[1082] DOTA-Cmp-Thr-Aib-Ptf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-NH2(PSM-0549);

[1083] Ac-Thr-Aib-Ptf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0550);

[1084] Ac-Thr-Aib-Mff-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0551);

[1085] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-NH2(PSM-0552);

[1086] DOTA-Cmp-Thr-Aib-Mff-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-NH2(PSM-0553);

[1087] Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Throl-OH(PSM-0554);

[1088] Ac-Thr-Aib-Mnf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0555);

[1089] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Phe-NH2(PSM-0556);

[1090] Ac-Thr-Aib-Ocf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0558);

[1091] Ac-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0559);

[1092] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Npg-NH2(PSM-0560);

[1093] Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Thr-Ala-NH2(PSM-0562);

[1094] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Glu-Cys]-Tle-Thr-NH2(PSM-0563);

[1095] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0565);

[1096] Ac-Thr-Aib-Phe-[Smc-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-NH2 (or: Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Ala-Asn-Smc]-Tle-Thr-Asp-NH2) (PSM-0567);

[1097] Hex-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-Ttds-lys(DOTA)-NH2 (PSM-0568);

[1098] Ac-Thr-Aib-Pcf-[Cys-Lys-Arg(Ac)-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0569);

[1099] Ac-Thr-Aib-Pcf-[Cys-Nle-Arg(Ac)-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0570);

[1100] nBuCAyl-Thr-Aib-Mcf-[Cys-Lys-Opy-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2 (PSM-0571);

[1101] DOTA-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0573);

[1102] DOTA-Pamb-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Bal-NH2 (PSM-0574);

[1103] Bio-Ttds-Ttds-Thr-Aib-Pcr-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0575);

[1104] Hex-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Ttds-lys(DOTA)-NH2 (PSM-0576);

[1105] HO-Succinyl-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0577);

[1106] Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Nle-Thr-Asp-NH2(PSM-0578);

[1107] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg(EtCAyl)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0579);

[1108] DOTA-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0580);

[1109] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Lys(DOTA-Ahx)-Asn-Cys]-Tle-Thr-NH2(PSM-0582);

[1110] DOTA-Cmp-Thr-Aib-Mcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0583);

[1111] Ac-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Leu-Cys]-Tle-Thr-NH2(PSM-0584);

[1112] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Ala-Nmn-Cys]-Tle-Thr-NH2(PSM-0585);

[1113] Ac-Thr-Aib-Trp-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0587);

[1114] Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Trp-Cys]-Tle-Thr-NH2(PSM-0589);

[1115] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-RMe2a-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0590):

[1116] Macropa-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0591);

[1117] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-RMel-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0592);

[1118] DOTAM-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0593);

[1119] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-OH (PSM-0594);

[1120] LSC-CmP-Thr-Aib-Pcf-[Cys-Iys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0601);

[1121] DOTA-CmP-Thr-Aib-Phe-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-en-H (PSM-0605) and

[1122] DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-Bal-NH2 (PSM-0606).

[1123] Implementation Plan 182. Implementation Plan 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56、57、58、59、60、61、62、63、64、65、66、67、68、69、70、71、72、73、74、75、76、77、78、79、80、81、82、83、84、85、86、87、88、89、90、91、92、93、94、95、96、97、98、99、100、101、102、103、104、105、106、107、108 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180 and 181, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the compound is capable of binding to PSMA.

[1124] Implementation Plan 183. Implementation Plan 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 11 0, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 1 53, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181 and 182, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the compound comprises a diagnostically active nuclide or a therapeutically active nuclide.

[1125] Embodiment 184. The compound of Embodiment 183, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the compound comprises a diagnostically active nuclide.

[1126] Embodiment 185. The compound of Embodiment 184, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the diagnostically active nuclide is a diagnostically active radionuclide.

[1127] Embodiment 186. The compound of embodiment 185 or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the diagnostically active radionuclide is selected from 43 Sc, 44 Sc, 51 Mn, 52 Mn,64 Cu, 67 Ga, 68 Ga, 86 Y. 89 Zr, 94m Tc, 99m Tc, 111 In, 152 Tb, 155 Tb, 177 Lu, 201 Tl, 203 Pb, 18 F. 76 Br, 77 Br, 123 I. 124 I and 125 I.

[1128] Embodiment 187. The compound of Embodiment 186, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the diagnostically active radionuclide is selected from: 18 F. 43 Sc, 44 Sc, 64 Cu, 67 Ga, 68 Ga, 86 Y. 89 Zr, 99m Tc, 111 In, 152 Tb, 155 Tb and 203 Pb.

[1129] Embodiment 188. The compound of embodiment 187 or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the diagnostically active radionuclide is selected from 18 F. 64 Cu, 68 Ga and 111 In.

[1130] Implementation Plan 189. Implementation Plans 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56 ,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152 2, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, and 183, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the compound comprises a therapeutically active nuclide.

[1131] Embodiment 190. The compound of Embodiment 189, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the therapeutically active nuclide is a therapeutically active radionuclide.

[1132] Embodiment 191. The compound of embodiment 190 or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the therapeutically active radionuclide is selected from 47 Sc, 67 Cu, 89 Sr. 90 Y. 111 In, 153 Sm, 149 Tb, 161 Tb, 177 Lu,186 Re、 188 Re、 212 Pb, 212 Bi, 213 Bi, 223 Ra, 224 Ra, 225 Ac, 226 Th, 227 Th, 131 I and 211 At.

[1133] Embodiment 192. The compound of embodiment 191 or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the therapeutically active radionuclide is selected from 47 Sc, 67 Cu, 90 Y. 161 Tb, 177 Lu, 188 Re、 212 Pb, 212 Bi, 213 Bi, 225 Ac and 227 Th.

[1134] Embodiment 193. The compound of embodiment 192 or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the therapeutically active radionuclide is selected from 90 Y. 161 Tb, 177 Lu, 212 Pb, 225 Ac and 227 Th.

[1135] Implementation Plan 194. Implementation Plans 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57 , 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111 1, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154 , 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187 and 188, or a pharmaceutically acceptable salt, solvate or hydrate thereof, for use in a method of diagnosing a disease.

[1136] Implementation Plan 195. Implementation Plans 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57 , 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111 1, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154 , 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 189, 190, 191, 192 and 193, or a pharmaceutically acceptable salt, solvate or hydrate thereof, for use in a method of treating a disease.

[1137] Embodiment 196. The compound of any one of Embodiments 194 and 195, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the disease is a disease involving the prostate-specific membrane antigen (PSMA) protein.

[1138] Embodiment 197. The compound of any one of Embodiments 194, 195 and 196, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the disease involves cells showing upregulated expression of prostate-specific membrane antigen (PSMA), preferably a diseased tissue comprising cells showing upregulated expression of PSMA.

[1139] Embodiment 198. The compound of any one of Embodiments 194, 195, 196 and 197, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the disease is a neoplasm, preferably a cancer or a tumor.

[1140] Embodiment 199. The compound for use in embodiment 198 or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the tumor is selected from the group consisting of an advanced tumor, a metastatic tumor and a primary tumor.

[1141] Embodiment 200. A compound for use in any one of embodiments 198 and 199, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the tumor is selected from the group consisting of a prostate tumor, a metastatic prostate tumor, a lung tumor, a kidney tumor, a glioblastoma, a pancreatic tumor, a bladder tumor, a sarcoma, a melanoma, a breast tumor, a colon tumor, a pheochromocytoma, an esophageal tumor, a gastric tumor, a carcinoma, a squamous cell carcinoma (e.g., of the cervix, eyelid, conjunctiva, vagina, lung, oral cavity, skin, bladder, tongue, larynx and esophagus) and adenocarcinoma (e.g., of the prostate, small intestine, endometrium, cervix, large intestine, lung, pancreas, esophagus, rectum, uterus, stomach, breast and ovary), and combinations thereof.

[1142] Embodiment 201. The compound of embodiment 200, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the tumor is a prostate tumor or a metastatic prostate tumor.

[1143] Embodiment 202. A compound for use in embodiment 198, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the cancer is selected from the group consisting of prostate cancer (e.g., metastatic castration-resistant prostate cancer), kidney cancer (e.g., clear cell carcinoma), head cancer, neck cancer, head and neck cancer, lung cancer (e.g., non-small cell lung cancer), salivary gland cancer, breast cancer, colorectal cancer, esophageal cancer, stomach cancer, liver cancer (e.g., hepatocellular carcinoma), thyroid cancer, glioblastoma, glioma, gallbladder cancer, laryngeal cancer, leukemia / lymphoma, uterine cancer, skin cancer (e.g., melanoma), endocrine cancer, sarcoma, urethral cancer, pancreatic cancer, gastrointestinal cancer, ovarian cancer, cervical cancer, endometrial cancer, fallopian tube cancer, primary peritoneal cancer, blood cancer (e.g., diffuse large B-cell lymphoma, Hodgkin lymphoma, non-Hodgkin lymphoma, follicular lymphoma, acute myeloid leukemia, or multiple myeloma), cancer of unknown primary site, adenoma, and tumor neovascularization.

[1144] Embodiment 203. The compound of embodiment 202, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the cancer is prostate cancer.

[1145] Embodiment 204. A compound for use in any one of embodiments 194, 196, 197, 198, 199, 200, 201, 202 and 203, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the compound comprises a diagnostically active nuclide, preferably a diagnostically active radionuclide.

[1146] Embodiment 205. The compound for use in embodiment 204, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the diagnostically active nuclide is selected from: 43 Sc, 44 Sc, 51 Mn, 52 Mn, 64 Cu, 67 Ga, 68 Ga, 86 Y. 89 Zr, 94m Tc, 99m Tc, 111 In, 152 Tb, 155 Tb, 177 Lu, 201 Tl, 203 Pb, 18 F. 76 Br, 77 Br, 123 I. 124 I. 125 1, preferably 18 F. 43 Sc, 44 Sc, 64 Cu, 67 Ga, 68 Ga, 86 Y. 89 Zr, 99m Tc, 111 In, 152 Tb, 155 Tb, 203 Pb, more preferably 18 F. 64 Cu, 68 Ga and 111 In.

[1147] Embodiment 206. The compound of any one of embodiments 194 and 196, 197, 198, 199, 200, 201, 202, 203, 204 and 205, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the method for diagnosis is an imaging method.

[1148] Embodiment 207. The compound of embodiment 206, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the imaging method is selected from scintigraphy, single photon emission computed tomography (SPECT), positron emission tomography (PET), SPECT / computed tomography, PET / computed tomography, and combinations thereof.

[1149] Embodiment 208. A compound for use in any one of embodiments 194, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, and 207, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the method comprises administering a diagnostically effective amount of the compound to a subject, preferably a mammal, wherein the mammal is selected from humans, companion animals, pets, and livestock, more preferably, the subject is selected from humans, dogs, cats, horses, and cows, and most preferably, the subject is a human.

[1150] Embodiment 209. A compound for use in any one of embodiments 195, 196, 197, 198, 199, 200, 201, 202 and 203, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the compound comprises a therapeutically active nuclide, preferably a therapeutically active radionuclide.

[1151] Embodiment 210. The compound of embodiment 209 or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the therapeutically active nuclide is selected from: 47 Sc, 67 Cu, 89 Sr. 90 Y. 111 In, 153 Sm, 149 Tb, 161 Tb, 177 Lu, 186 Re、 188 Re、 212 Pb, 212 Bi, 213 Bi, 223 Ra, 224 Ra, 225 Ac, 226 Th, 227 Th, 131 I. 211 At, preferred 47 Sc, 67 Cu, 90 Y. 161 Tb, 177 Lu, 188 Re、 212 Pb,212 Bi, 213 Bi, 225 Ac, 227 Th, more preferably 90 Y. 161 Tb, 177 Lu, 212 Pb, 225 Ac and 227 Th.

[1152] Embodiment 211. A compound for use in any one of embodiments 195, 196, 197, 198, 199, 200, 201, 202, 203, 209 and 210, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the method comprises administering a therapeutically effective amount of the compound to a subject, preferably a mammal, wherein the mammal is selected from humans, companion animals, pets and livestock, more preferably, the subject is selected from humans, dogs, cats, horses and cows, and most preferably, the subject is a human.

[1153] Implementation Plan 212. Implementation Plan 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60 0, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115 5, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160 , 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 204 and 205, or a pharmaceutically acceptable salt, solvate or hydrate thereof, for use in a method of identifying a subject wherein the subject may or may not respond to treatment for a disease,wherein the method of identifying a subject comprises using embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62 , 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 1 21, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 1 70, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 204 and 205, or a pharmaceutically acceptable salt, solvate or hydrate thereof, for use in a diagnostic method, preferably for use in a method for diagnosing a disease as described in any one of embodiments 194, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207 and 208. ,

[1154] Implementation Plan 213. Implementation Plans 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60 , 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 1 16、117、118、119、120、121、122、123、124、125、126、127、128、129、130、131、132、133、134、135、136、137、138、139、140、141、142、143、144、145、146、147、148、149、150、151、152、153、154、155、156、157、158、159、160、161、 A compound of any one of 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 204, and 205, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, for use in a method of selecting a subject from a group of subjects, wherein the subject may or may not respond to treatment for a disease,wherein the method for selecting a subject from a group of subjects comprises using embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60 , 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169 9, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 204 and 205, or a pharmaceutically acceptable salt, solvate or hydrate thereof, for use in a diagnostic method, preferably for use in a method for diagnosing a disease as described in any one of embodiments 194, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207 and 208. ,

[1155] Implementation Plan 214. Implementation Plan 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61 1, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 1 17, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 1 A method of stratifying a group of subjects into subjects who are likely to respond to a treatment for a disease and subjects who are likely not to respond to a treatment for a disease,wherein the method for stratifying a group of subjects comprises using embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81 1, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120 0, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 204 and 205, or a pharmaceutically acceptable salt, solvate or hydrate thereof, for use in a diagnostic method, preferably for use in a method for diagnosing a disease as described in any one of embodiments 194, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207 and 208. ,

[1156] Embodiment 215. The compound for use in any one of embodiments 212, 213 and 214, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the disease is a disease involving the prostate specific membrane antigen (PSMA) protein.

[1157] Embodiment 216. A compound for use in any one of embodiments 212, 213, 214 and 215, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the disease involves cells that show upregulated expression of prostate specific membrane antigen (PSMA).

[1158] Embodiment 217. The compound according to any one of embodiments 212, 213, 214, 215 and 216, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the disease is a neoplasm, preferably a cancer or a tumor.

[1159] Embodiment 218. A compound for use in embodiment 217, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the tumor is selected from the group consisting of a prostate tumor, a metastatic prostate tumor, a lung tumor, a kidney tumor, a glioblastoma, a pancreatic tumor, a bladder tumor, a sarcoma, a melanoma, a breast tumor, a colon tumor, a pheochromocytoma, an esophageal tumor, a gastric tumor, a carcinoma, a squamous cell carcinoma (e.g., of the cervix, eyelid, conjunctiva, vagina, lung, oral cavity, skin, bladder, tongue, larynx, and esophagus), and adenocarcinoma (e.g., of the prostate, small intestine, endometrium, cervix, large intestine, lung, pancreas, esophagus, rectum, uterus, stomach, breast, and ovary), and combinations thereof.

[1160] Embodiment 219. The compound of embodiment 218 or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the tumor is a prostate tumor or a metastatic prostate tumor.

[1161] Embodiment 220. A compound for use in embodiment 217, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the tumor, cancer, and tumour are each independently selected from prostate cancer (e.g., metastatic castration-resistant prostate cancer), renal cancer (e.g., clear cell carcinoma), head cancer, neck cancer, head and neck cancer, lung cancer (e.g., non-small cell lung cancer), salivary gland cancer, breast cancer, colorectal cancer, esophageal cancer, gastric cancer, liver cancer (e.g., hepatocellular carcinoma), thyroid cancer, glioblastoma Cancers of the uterus, gliomas, gallbladder, laryngeal, leukemia / lymphoma, uterine, skin (e.g., melanoma), endocrine, sarcomas, urethral, ​​pancreatic, gastrointestinal, ovarian, cervical, endometrial, fallopian tube, primary peritoneal, hematologic (e.g., diffuse large B-cell, Hodgkin, non-Hodgkin, follicular, acute myeloid leukemia, or multiple myeloma), cancer of unknown primary, adenomas, and tumor neovascularization.

[1162] Embodiment 221. The compound of embodiment 220, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the cancer is prostate cancer.

[1163] Embodiment 222. A compound for use in any one of Embodiments 212, 213, 214, 215, 216, 217, 218, 219, 220, and 221, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the diagnostic method is an imaging method.

[1164] Embodiment 223. A compound for use in Embodiment 222, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the imaging method is selected from scintigraphy, single photon emission computed tomography (SPECT), positron emission tomography (PET), SPECT / computed tomography, PET / computed tomography, and combinations thereof.

[1165] Embodiment 224. A compound for use in any one of embodiments 212, 213, 214, 215, 216, 217, 218, 219, 220 and 221, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the compound comprises a diagnostically active nuclide, preferably a diagnostically active radionuclide.

[1166] Embodiment 225. The compound of embodiment 224 or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the diagnostically active nuclide is selected from: 43 Sc, 44 Sc, 51 Mn, 52 Mn, 64 Cu, 67 Ga, 68 Ga, 86 Y. 89 Zr, 94m Tc, 99m Tc, 111 In, 152 Tb, 155 Tb, 177 Lu, 201 Tl, 203 Pb, 18 F. 76 Br, 77 Br, 123 I. 124 I and 125 I, preferably selected from 18 F. 43 Sc, 44 Sc, 64 Cu, 67 Ga, 68 Ga, 86 Y. 89 Zr, 99m Tc, 111 In, 152Tb, 155 Tb and 203 Pb, more preferably selected from 18 F. 64 Cu, 68 Ga and 111 In.

[1167] Implementation Plan 226. Implementation Plan 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62 2, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118 8, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 1 A compound of any one of 190, 191, 192, and 193, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, for use in a method of delivering a diagnostically active radionuclide or a therapeutically active radionuclide to prostate-specific membrane antigen (PSMA).

[1168] Embodiment 227. The compound of embodiment 226 or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the diagnostically active radionuclide is selected from 43 Sc, 44 Sc,51 Mn, 52 Mn, 64 Cu, 67 Ga, 68 Ga, 86 Y. 89 Zr, 94m Tc, 99m Tc, 111 In, 152 Tb, 155 Tb, 177 Lu, 201 Tl, 203 Pb, 18 F. 76 Br, 77 Br, 123 I. 124 I and 125 I, preferably selected from 18 F. 43 Sc, 44 Sc, 64 Cu, 67 Ga, 68 Ga, 86 Y. 89 Zr, 99m Tc, 111 In, 152 Tb, 155 Tb, and 203 Pb, more preferably selected from 18 F. 64 Cu, 68 Ga and 111 In.

[1169] Embodiment 228. The compound of embodiment 226 or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the therapeutically active radionuclide is selected from 47 Sc, 67 Cu, 89 Sr. 90 Y. 111 In, 153 Sm, 149 Tb, 161 Tb, 177 Lu, 186 Re、 188 Re、 212 Pb, 212 Bi, 213 Bi, 223 Ra, 224 Ra, 225 Ac, 226 Th, 227 Th,131 I. 211 At is preferably selected from 47 Sc, 67 Cu, 90 Y. 161 Tb, 177 Lu, 188 Re、 212 Pb, 212 Bi, 213 Bi, 225 Ac, 227 Th, more preferably selected from 90 Y. 161 Tb, 177 Lu, 212 Pb, 225 Ac and 227 Th.

[1170] Embodiment 229. A compound for use in any one of embodiments 226-228, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the prostate-specific membrane antigen (PSMA) is expressed by cells, preferably prostate cells, metastatic prostate cells, lung cells, kidney cells, pancreatic cells, bladder cells, breast cells, colon cells, germ cells, esophageal cells, gastric cells, endothelial cells, and combinations thereof, each of which exhibits upregulated PSMA expression.

[1171] Embodiment 230. The compound of embodiment 229 or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the cell is contained in or is part of a tissue, preferably a diseased tissue of a subject suffering from a disease.

[1172] Embodiment 231. A compound for use in Embodiment 230, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the disease involves cells exhibiting upregulated PSMA expression, preferably a diseased tissue containing cells exhibiting upregulated PSMA expression.

[1173] Embodiment 232. The compound according to any one of embodiments 230 and 231, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the disease is a neoplasm, preferably a cancer or a tumor.

[1174] Embodiment 233. A compound for use in embodiment 232, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the tumor is selected from the group consisting of a prostate tumor, a metastatic prostate tumor, a lung tumor, a kidney tumor, a glioblastoma, a pancreatic tumor, a bladder tumor, a sarcoma, a melanoma, a breast tumor, a colon tumor, a pheochromocytoma, an esophageal tumor, a gastric tumor, a carcinoma, a squamous cell carcinoma (e.g., of the cervix, eyelid, conjunctiva, vagina, lung, oral cavity, skin, bladder, tongue, larynx, and esophagus), and adenocarcinoma (e.g., of the prostate, small intestine, endometrium, cervix, large intestine, lung, pancreas, esophagus, rectum, uterus, stomach, breast, and ovary), and combinations thereof.

[1175] Embodiment 234. A compound for use in embodiment 232, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein the cancer is selected from prostate cancer (e.g., metastatic castration-resistant prostate cancer), kidney cancer (e.g., clear cell carcinoma), head cancer, neck cancer, head and neck cancer, lung cancer (e.g., non-small cell lung cancer), salivary gland cancer, breast cancer, colorectal cancer, esophageal cancer, stomach cancer, liver cancer (e.g., hepatocellular carcinoma), thyroid cancer, glioblastoma, glioma, gallbladder cancer, laryngeal cancer, leukemia / lymphoma, uterine cancer, skin cancer (e.g., melanoma), endocrine cancer, sarcoma, urethral cancer, pancreatic cancer, gastrointestinal cancer, ovarian cancer, cervical cancer, endometrial cancer, fallopian tube cancer, primary peritoneal cancer, blood cancer (e.g., diffuse large B-cell lymphoma, Hodgkin lymphoma, non-Hodgkin lymphoma, follicular lymphoma, acute myeloid leukemia, or multiple myeloma), cancer of unknown primary site, adenoma, and tumor neovascularization.

[1176] Embodiment 235. The compound of any one of Embodiments 186-188, 205, 225 and 227, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the diagnostically active nuclide is 18 F, wherein the diagnostically active nuclide is bound to aluminum, wherein the aluminum is bound to a chelating agent and 18 F combination.

[1177] Embodiment 236. A composition, preferably a pharmaceutical composition, wherein the composition comprises the method according to embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114 、115、116、117、118、119、120、121、122、123、124、125、126、127、128、129、130、131、132、133、134、135、136、137、138、139、140、141、142、143、144、145、146、147、148、149、150、151、152、153、154、155、156、157、158、159、160、161、16 2, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 205, 210, 224, 225, 227 and 228, or a pharmaceutically acceptable salt, solvate or hydrate thereof, and a pharmaceutically acceptable excipient.

[1178] Embodiment 237. The composition of embodiment 236, for use in any method defined in any preceding embodiment.

[1179] Embodiment 238. A method of diagnosing a disease in a subject, wherein the method comprises administering to the subject a diagnostically effective amount of a method according to embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106、107、108、109、110、111、112、113、114、115、116、117、118、119、120、121、122、123、124、125、126、127、128、129、130、131、132、133、134、135、136、137、138、139、140、141、142、143、144、145、146、147、148、149、150、 184, 185, 186, 187, and 188, or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

[1180] Embodiment 239. The method of embodiment 238, wherein the compound or a pharmaceutically acceptable salt, solvate or hydrate thereof comprises a diagnostically active nuclide, wherein the nuclide is preferably a diagnostically active radionuclide.

[1181] Embodiment 240. A method of treating a disease in a subject, wherein the method comprises administering to the subject a therapeutically effective amount of a drug according to Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83 7, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149 9, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 189, 190, 191, 192 and 193, or a pharmaceutically acceptable salt, solvate or hydrate thereof.

[1182] Embodiment 241. The method of embodiment 240, wherein the compound or a pharmaceutically acceptable salt, solvate or hydrate thereof comprises a therapeutically active nuclide, wherein the nuclide is preferably a therapeutically active radionuclide.

[1183] Embodiment 242. The method of any one of embodiments 238, 239, 240 and 241, wherein the disease is a disease involving the prostate-specific membrane antigen (PSMA) protein.

[1184] Embodiment 243. The method of any one of embodiments 238, 239, 240, 241 and 242, wherein the disease involves cells showing upregulated expression of prostate-specific membrane antigen (PSMA), preferably a diseased tissue comprising cells showing upregulated expression of PSMA.

[1185] Embodiment 244. A kit comprising the invention according to embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65 3, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122 2, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172 2, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 205, 210, 224, 225, 227 and 228, or a pharmaceutically acceptable salt, solvate or hydrate thereof, one or more optional excipients, and optionally one or more devices, wherein the device is selected from a labeling device, a purification device, a processing device, a radiation protection device, an analytical device or an administration device.

[1186] Embodiment 245. The kit of embodiment 244, for use in any method as defined in any of the preceding embodiments.

[1187] Implementation Plan 246. Implementation Plan 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164 4, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194 and 195, or a pharmaceutically acceptable salt, solvate or hydrate thereof in the preparation of a medicament or for the preparation of a medicament, preferably for the treatment of a disease disclosed herein.

[1188] Implementation Plan 247. Implementation Plan 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62 2, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118 、119、120、121、122、123、124、125、126、127、128、129、130、131、132、133、134、135、136、137、138、139、140、141、142、143、144、145、146、147、148、149、150、151、152、153、154、155、156、157、158、159、160、161、162、163、164、16 5, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194 and 195, or a pharmaceutically acceptable salt, solvate or hydrate thereof, in the preparation of a diagnostic tool or for the preparation of a diagnostic tool, preferably a diagnostic tool for diagnosing a disease disclosed herein.

[1189] It will be appreciated by those skilled in the art that the compounds of the present application are any compounds disclosed herein, including but not limited to any compound described in any of the above embodiments and any of the following embodiments.

[1190] It should be recognized by those skilled in the art that the methods of the present application are any methods disclosed herein, including but not limited to any method described in any of the above embodiments and any of the following embodiments.

[1191] It should be recognized by those skilled in the art that the composition of the present application is any composition disclosed herein, including but not limited to any composition described in any of the above embodiments and any of the following embodiments.

[1192] Those skilled in the art will recognize that the kit of the present application is any kit disclosed herein, including but not limited to any kit described in any of the above embodiments and any of the following embodiments.

[1193] Those skilled in the art will recognize that the expression “aspects of the present application” are used synonymously with the terms “aspects of the invention” and “aspects of the invention,” respectively, and that the expression “embodiments of the present application” are used synonymously with the terms “embodiments of the invention” and “embodiments of the invention,” respectively.

[1194] Unless otherwise indicated, all numbers used in this application to express quantities, conditions, etc. should be understood to be modified by the term "about" in all cases. Therefore, unless otherwise indicated, the numerical parameters set forth in this application are approximate values, which may vary depending on the desired properties sought to be obtained by the application. At the very least, and not to be considered as an attempt to limit the application of the doctrine of equivalents, each numerical parameter should be interpreted according to the number of significant figures and ordinary rounding conventions.

[1195] In addition, the disclosure of numerical ranges within this application is considered to be a disclosure of all values ​​and ranges within that range. For example, if a range is from 1 to 10, it is considered to include, for example, 1, 2, 2.2, 3, 4, 5, 6, 7, 7.4, 7.6, 8, 8.7, 9, 9.5, 10 or any other value or range (integer or non-integer) within that range. In addition, as used herein, the term "at least" includes the stated number, for example, "at least 50" includes 50.

[1196] As preferably used herein, the expression alkyl refers each independently to a saturated straight or branched chain hydrocarbon radical and is usually accompanied by a qualifier specifying the number of carbon atoms it may contain. For example, the expression (C1-C6)alkyl refers each independently to methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 1-methyl-butyl, 1-ethyl-propyl, 3-methyl-butyl, 1,2-dimethyl-propyl, 2-methyl-butyl, 1,1-dimethyl-propyl, 2,2-dimethylpropyl, n-hexyl, 1,1-dimethyl-butyl and each of any other isomers of alkyl groups containing six saturated carbon atoms.

[1197] In one embodiment and as preferably used herein, "(C1-C2)alkyl" refers to each and either of methyl and ethyl.

[1198] In one embodiment, and as preferably used herein, "(C1-C3)alkyl" refers to each and any one of methyl, ethyl, n-propyl and isopropyl.

[1199] In one embodiment and as preferably used herein, "(C1-C4)alkyl" refers to each and any one of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl.

[1200] In one embodiment and as preferably used herein, “(C1-C6)alkyl” refers to methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 2-methyl-butyl, 3-methyl-butyl, 3-pentyl, 3-methyl-but-2-yl, 2-methyl-but-2-yl, 2,2-dimethylpropyl, n-hexyl, 2-hexyl, 2-methyl-pentyl, 3-methyl-pentyl, Each and any one of 4-methyl-pentyl, 3-hexyl, 2-ethyl-butyl, 2-methyl-pent-2-yl, 2,2-dimethyl-butyl, 3,3-dimethyl-butyl, 3-methyl-pent-2-yl, 4-methyl-pent-2-yl, 2,3-dimethyl-butyl, 3-methyl-pent-3-yl, 2-methyl-pent-3-yl, 2,3-dimethyl-but-2-yl and 3,3-dimethyl-but-2-yl.

[1201] In one embodiment, and as preferably used herein, "(C1-C8)alkyl" refers to a saturated or unsaturated, straight-chain or branched hydrocarbon group having 1 to 8 carbon atoms. Representative (C1-C8)alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 2-methyl-butyl, 3-methyl-butyl, 3-pentyl, 3-methyl-but-2-yl, 2-methyl-but-2-yl, 2,2-dimethylpropyl, n-hexyl, 2-hexyl, 2-methyl-pentyl, 3-methyl-pentyl, 4-methyl-pentyl, 3-hexyl, 2-ethyl-butyl, 2-methyl-pent-2-yl, 2,2-dimethyl-butyl, 3,3-dimethyl-butyl, 3-methyl-pent-2-yl, 4-methyl-pent-2-yl, 2,3-dimethyl methyl-butyl, 3-methyl-pentan-3-yl, 2-methyl-pentan-3-yl, 2,3-dimethyl-butan-2-yl, 3,3-dimethyl-butan-2-yl, n-heptyl, 2-heptyl, 2-methyl-hexyl, 3-methyl-hexyl, 4-methyl-hexyl, 5-methyl-hexyl, 3-heptyl, 2-ethyl-pentyl, 3-ethyl-pentyl, 4-heptyl, 2-methyl-hexan-2-yl, 2,2-dimethyl-pentyl, 3,3-dimethyl-pentyl, 4,4-dimethyl-pentyl, 3-methyl-hexan-2-yl, 4-methyl-hexan-2-yl, 5-methyl-hexan-2-yl, 2,3-dimethyl-pentyl, 2,4-dimethyl 2-ethyl-2-methyl-butyl, 4-methyl-hexan-3-yl, 5-methyl-hexan-3-yl, 2-ethyl-3-methyl-butyl, 2,3-dimethyl-pentan-2-yl, 2,4-dimethyl-pentan-2-yl, 3,3-dimethyl-pentan-2-yl, 4,4-dimethyl-pentan-2-yl, 2,2,3-trimethyl-butyl, 2,3,3-trimethyl-butyl, 2,3,3-trimethyl-butan-2-yl, n-octyl, 2-octyl, 2-methyl-heptyl, 3-methyl-heptyl, 4-methyl-heptyl, 5-methyl-heptyl, 6-methyl-heptyl, 4-Dimethyl-hexyl, 5-Methyl-heptyl, 6-Methyl-heptyl, 2,3-Dimethyl-hexyl, 2,4-Dimethyl-hexyl, 2,5-Dimethyl-hexyl, 3,4-Dimethyl-hexyl, 3,5-Dimethyl-hexyl, 3,4-Dimethyl-hexyl, 4,5-Dimethyl-heptyl, 2,3-Dimethyl-hexan-1-yl, 2,4-Dimethyl-hexan-1-yl, 2,5-Dimethyl-hexan-1-yl, 3,4-Dimethyl-hexan-1-yl, 3,5-Dimethyl-hexan-1-yl, 3,5-dimethyl-hexan-1-yl, 3-methyl-heptan-3-yl, 2-ethyl-2-methyl-1-yl, 3-ethyl-3-methyl-1-yl, 4-methyl-heptan-3-yl, 5-methyl-heptan-3-yl, 6-methyl-heptan-3-yl, 2-ethyl-3-methyl-pentyl, 2-ethyl-4-methyl-pentyl, 3-ethyl-4-methyl-pentyl, 2,3-dimethyl-hexan-2-yl, 2,4-dimethyl-hexan-2-yl, 2,5-dimethyl-hexan-2-yl, 3,3-dimethyl-hexan- 2-yl, 3,4-dimethyl-hexan-2-yl, 3,5-dimethyl-hexan-2-yl, 4,4-dimethyl-hexan-2-yl, 4,5-dimethyl-hexan-2-yl, 5,5-dimethyl-hexan-2-yl, 2,2,3-trimethyl-pentyl, 2,2,4-trimethyl-pentyl, 2,3,3-trimethyl-pentyl, 2,3,4-trimethyl-pentyl, 2,4,4-trimethyl-pentyl, 3,3,4-trimethyl-pentyl, 3,4,4-trimethyl-pentyl, 2,3,3-trimethyl- Pentan-2-yl, 2,3,4-trimethyl-pentan-2-yl, 2,4,4-trimethyl-pentan-2-yl, 3,4,4-trimethyl-pentan-2-yl, 2,2,3,3-tetramethyl-butyl, 3,4-dimethyl-hexan-3-yl, 3,5-dimethyl-hexan-3-yl, 4,4-dimethyl-hexan-3-yl, 4,5-dimethyl-hexan-3-yl, 5,5-dimethyl-hexan-3-yl, 3-ethyl-3-methyl-pentan-2-yl, 3-ethyl-4-methyl-pentan-2-yl, 3-ethyl -hexan-3-yl, 2,2-diethyl-butyl, 3-ethyl-3-methyl-pentyl, 4-ethyl-hexan-3-yl, 5-methyl-hept-3-yl, 2-ethyl-3-methyl-pentyl, 4-methyl-hept-4-yl, 3-methyl-hept-4-yl, 2-methyl-hept-4-yl, 3-ethyl-hexan-2-yl, 2-ethyl-2-methyl-pentyl, 2-isopropyl-pentyl, 2,2-dimethyl-hexan-3-yl, 2,2,4-trimethyl-pentan-3-yl and 2-ethyl-3-methyl-pentyl. (C1-C8)alkyl may be unsubstituted or substituted with one or more groups including, but not limited to, (C1-C8)alkyl, -O-[(C1-C8)alkyl], -aryl, -CO-R', -O-CO-R', -CO-OR', -CO-NH2, -CO-NHR', -CO-NR'2, -NH-CO-R', -SO2-R', -SO-R', -OH, -halogen, -N3, -NH2, -NHR', -NR'2, and -CN; wherein each R' is independently selected from -(C1-C8)alkyl and aryl.

[1202] In one embodiment and as preferably used herein, "(C2-C6)alkyl" each independently refers to ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 2-methyl-butyl, 3-methyl-butyl, 3-pentyl, 3-methyl-but-2-yl, 2-methyl-but-2-yl, 2,2-dimethylpropyl, n-hexyl, 2-hexyl, 2-methyl-pentyl, 3-methyl Any of 2-methyl-3-pentyl, 2-methyl-3-pentyl, 2-ethyl-butyl, 2-methyl-pent-2-yl, 2,2-dimethyl-butyl, 3,3-dimethyl-butyl, 3-methyl-pent-2-yl, 4-methyl-pent-2-yl, 2,3-dimethyl-butyl, 3-methyl-pent-3-yl, 2-methyl-pent-3-yl, 2,3-dimethyl-but-2-yl and 3,3-dimethyl-but-2-yl.

[1203] In one embodiment and as preferably used herein, “(C4-C6)alkyl” each independently refers to any one of n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 2-methyl-butyl, 3-methyl-butyl, 3-pentyl, 3-methyl-but-2-yl, 2-methyl-but-2-yl, 2,2-dimethylpropyl, n-hexyl, 2-hexyl, 2-methyl-pentyl, 3-methyl-pentyl, 4-methyl-pentyl, 3-hexyl, 2-ethyl-butyl, 2-methyl-pent-2-yl, 2,2-dimethyl-butyl, 3,3-dimethyl-butyl, 3-methyl-pent-2-yl, 4-methyl-pent-2-yl, 2,3-dimethyl-butyl, 3-methyl-pent-3-yl, 2-methyl-pent-3-yl, 2,3-dimethyl-but-2-yl and 3,3-dimethyl-but-2-yl.

[1204] In one embodiment, and as preferably used herein, "carbocycle" refers to a saturated, unsaturated or aromatic monocyclic or bicyclic carbocycle. The carbocycle may be unsubstituted or substituted by one or more groups including, but not limited to, (C1-C8)alkyl, -O-[(C1-C8)alkyl], -aryl, -CO-R', -O-CO-R', -CO-OR', -CO-NH2, -CO-NHR', -CO-NR'2, -NH-CO-R', -SO2-R', -SO-R', -OH, -halogen, -N3, -NH2, -NHR', -NR'2 and -CN; wherein each R' is independently selected from -(C1-C8)alkyl and aryl.

[1205] In one embodiment, and as preferably used herein, "heterocycle" refers to a saturated, unsaturated or aromatic monocyclic or bicyclic heterocycle. The heterocyclic group may be unsubstituted or substituted by one or more groups including, but not limited to, (C1-C8) alkyl, -O-[(C1-C8) alkyl], -aryl, -CO-R', -O-CO-R', -CO-OR', -CO-NH2, -CO-NHR', -CO-NR'2, -NH-CO-R', -SO2-R', -SO-R', -OH, -halogen, -N3, -NH2, -NHR', -NR'2 and -CN; wherein each R' is independently selected from -(C1-C8) alkyl and aryl.

[1206] In one embodiment, and as preferably used herein, "aryl" refers to a carbocyclic aromatic group. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, and anthracenyl.

[1207] In one embodiment, and as preferably used herein, "heteroaryl" refers to a heterocyclic aromatic group. Examples of heteroaryl groups include, but are not limited to, furan, thiophene, pyridine, pyrimidine, benzothiophene, benzofuran, and quinoline.

[1208] In one embodiment, and as preferably used herein, "(C5-C6)heteroaryl" refers to a heterocyclic aromatic group consisting of 5 or 6 ring atoms, at least one of which is not carbon, including, for example, nitrogen, sulfur, or oxygen. The heterocyclic aromatic group may be unsubstituted or substituted with one or more groups including, but not limited to, -(C1-C8)alkyl, -O-[(C1-C8)alkyl], -aryl, -CO-R', -O-CO-R', -CO-OR', -CO-NH2, -CO-NHR', -CO-NR'2, -NH-CO-R', -SO2-R', -SO-R', -OH, -halogen, -N3, -NH2, -NHR', -NR'2, and -CN; wherein each R' is independently selected from -(C1-C8)alkyl and aryl.

[1209] In one embodiment, and as preferably used herein, "amino acid residue" refers to all the atoms of an amino acid which remain after said amino acid has been bound to other amino acids in a peptide chain.

[1210] In one embodiment, and as preferably used herein, "side chain" refers to all atoms of an amino acid residue that are not contained in the "backbone" portion of the amino acid residue. "Backbone" refers to the structure formed by the continuous linkage of amino acids, in which the α-nitrogen atom of an α-amino acid, the β-nitrogen atom of a β-amino acid, the γ-nitrogen of a γ-amino acid residue, the δ-nitrogen atom of a δ-amino acid, the ε-nitrogen of an ε-amino acid, or the ω-nitrogen of an ω-amino acid is attached to the C1 carbonyl atom of the preceding amino acid.

[1211] In one embodiment, and as preferably used herein, an atom with an unspecified atomic mass number in any structural formula or in any paragraph of this specification is a naturally occurring mixture of isotopes or an individual isotope with an unspecified isotopic composition. This applies in particular to carbon, oxygen, nitrogen, sulfur, phosphorus, halogen, and metal atoms, including but not limited to C, O, N, S, F, P, Cl, Br, At, Sc, Cr, Mn, Co, Fe, Cu, Ga, Sr, Zr, Y, Mo, Tc, Ru, Rh, Pd, Pt, Ag, In, Sb, Sn, Te, I, Pr, Pm, Dy, Sm, Gd, Tb, Ho, Dy, Er, Yb, Tm, Lu, Sn, Re, Rd, Os, Ir, Au, Pb, Bi, Po, Fr, Ra, Ac, Th, and Fm.

[1212] In one embodiment, and as preferably used herein, a "chelator" is a compound capable of forming a chelate, wherein a chelate is a compound, including, for example, a cyclic compound, in which a metal or a moiety with an electronic energy gap or a lone pair of electrons participates in the formation of the ring. In certain embodiments, a chelator is a compound in which a single ligand occupies more than one coordination site at the central atom.

[1213] In one embodiment, and as preferably used herein, a "diagnostically active compound" is a compound that is suitable or useful for at least diagnosing a disease.

[1214] In one embodiment, and as preferably used herein, a "diagnostic agent" or "diagnostically active agent" is a compound that is suitable or useful for at least diagnosing a disease.

[1215] In one embodiment, and as preferably used herein, a "diagnostically active radionuclide" is a radionuclide that is suitable for or can be used to at least diagnose a disease. However, one skilled in the art will also recognize that the use of such diagnostically active radionuclides may not be limited to diagnostic purposes, but may encompass their use in therapy and theranostics.

[1216] In one embodiment, and as preferably used herein, a "therapeutically active compound" is a compound that is suitable or useful for at least treating a disease.

[1217] In one embodiment, and as preferably used herein, a "therapeutic agent" or "therapeutically active agent" is a compound that is suitable or useful for at least treating a disease.

[1218] In one embodiment, and as preferably used herein, a "therapeutically active radionuclide" is a radionuclide that is suitable for or can be used to at least treat a disease. However, one skilled in the art will also recognize that the use of such therapeutically active radionuclides may not be limited to therapeutic purposes, but may encompass their use in diagnosis and theranostics.

[1219] In one embodiment, and as preferably used herein, a "theranosticatively active compound" is a compound, which is suitable or useful for the diagnosis and treatment of a disease.

[1220] In one embodiment, and as preferably used herein, a "theranostic agent" or a "theranostic active agent" is a compound that is suitable or useful in the diagnosis and treatment of a disease.

[1221] In one embodiment, and as preferably used herein, a "theranostic active radionuclide" is a radionuclide which is suitable or useful for the diagnosis and treatment of a disease.

[1222] In one embodiment, and as preferably used herein, "theranostics" is a method for combined diagnosis and treatment of a disease. In certain embodiments, the active compound of the combined diagnosis and treatment used in the theranostics is radiolabeled.

[1223] In one embodiment, and as preferably used herein, "treatment of a disease" is the treatment and / or prevention of the disease.

[1224] In one embodiment, and as preferably used herein, the term "treating" is intended to include alleviating or eliminating the disorder, disease or condition; or one or more symptoms associated with the disorder, disease or condition; or alleviating or eradicating the cause of the disorder, disease or condition itself.

[1225] In one embodiment, and as preferably used herein, "preventing" describes the reduction or elimination of the occurrence of symptoms or complications of a disease, condition or disorder.

[1226] In one embodiment, and as preferably used herein, the term "subject" or "patient" includes mammals. The mammal can be, for example, any mammal, such as a human, companion animal, pet, livestock, dog, cat, horse, and cow.

[1227] In one embodiment, and as preferably used herein, a "disease involving the prostate-specific membrane antigen (PSMA) protein" is a disease involving cells that show upregulated expression of PSMA, which upregulated expression is causal to the disease and / or disease symptoms, or is part of the pathology underlying the disease.

[1228] In one embodiment, and as preferably used herein, a "target cell" or "target tissue" is a cell or tissue that expresses prostate-specific membrane antigen (PSMA) and is the cause of the disease and / or disease symptoms, or is part of the pathology underlying the disease.

[1229] In one embodiment, and as preferably used herein, a "non-target cell" or "non-target tissue" is a cell or tissue that does not express prostate-specific membrane antigen (PSMA) and / or that is not the cause of the disease and / or disease symptoms, or is not part of the pathology underlying the disease.

[1230] In one embodiment, and as preferably used herein, a "neoplasm" is an abnormal new growth of cells. The cells in a neoplasm grow faster than normal cells and will continue to grow if not treated. Neoplasms can be benign or malignant.

[1231] In one embodiment, and as preferably used herein, a "tumor" is a mass lesion that can be benign or malignant.

[1232] In one embodiment, and as preferably used herein, "cancer" is a malignant tumor.

[1233] In one embodiment, and as preferably used herein, "pharmaceutically acceptable excipients" refers to ingredients other than the active agent and / or active compound suitable for use in a pharmaceutical composition, including but not limited to pharmaceutically acceptable adjuvants, diluents, carriers, buffers, binders, colorants, lubricants, fillers, disintegrants, preservatives, surfactants and stabilizers.

[1234] In one embodiment, the disclosed compounds and compounds of the embodiments disclosed herein encompass pharmaceutically acceptable salts of such compounds, solvates of such compounds, or hydrates of such compounds.

[1235] In one embodiment, and as preferably used herein, "connection (linkage)" is the connection of two atoms of two independent parts. Preferred connection is a chemical bond or multiple chemical bonds. Preferably, the chemical bond is a covalent bond or multiple chemical bonds. Preferably, the connection is a covalent bond or a coordination bond. As preferably used herein, the embodiment of the coordination bond is a bond or a set of bonds achieved when the metal is bound by a chelating agent. Depending on the type of the atom connected and its atomic environment, different types of connections are produced. These types of connections are limited by the type of atomic arrangement produced by the connection. For example, the connection of the part comprising amine to the part comprising carboxylic acid results in a connection called amide (also referred to as amide bond, -CO-N-, -N-CO-). Those skilled in the art will recognize that this example and the following examples of the connection are only prototype examples and do not limit the scope of the application in any way. Those skilled in the art will recognize that the connection of the part comprising isothiocyanate to the part comprising amine results in thiourea (also referred to as thiourea bond, -N-CS-N-), and the connection of the part comprising C atom to the part comprising thiol group (-C-SH) results in thioether (also referred to as thioether bond, -CSC). Table 1 presents a non-limiting list of examples of linkages that can be used in conjunction with chelating agents and the remainder of the compounds of the present application and their characteristic atomic arrangements of the type.

[1236] Table 1:

[1237]

[1238] In some embodiments of the present application, examples of reactive groups used to form a connection between the chelating agent and the rest of the compound of the present application are summarized in Table 2. However, those skilled in the art will understand that such connections or reactive groups used to form the compounds of the present application are not limited to those in Table 2.

[1239] Table 2:

[1240]

[1241]

[1242] In one embodiment, and as preferably used herein, the term "activated carboxylic acid" refers to a carboxylic acid group having the general formula -CO-X, where X is a leaving group. For example, activated forms of the carboxylic acid group may include, but are not limited to, acid chlorides, symmetrical or asymmetrical anhydrides and esters. In some embodiments, the activated carboxylic acid group is an ester having pentafluorophenol, nitrophenol, benzotriazole, azabenzotriazole, thiophenol, ethyl 2-cyano-2-(hydroxyimino)acetate, or N-hydroxysuccinimide (NHS) as a leaving group.

[1243] In one embodiment, and as preferably used herein, the term "mediating a connection" refers to establishing a connection or establishing a type of connection, preferably a connection between two moieties.

[1244] The compounds of the present application may comprise the amino acid sequences provided herein. Conventional amino acids (also known as natural amino acids) are identified according to their standard three-letter codes and single-letter abbreviations, as shown in Table 3.

[1245] Table 3: Common amino acids and their abbreviations

[1246]

[1247]

[1248] Unconventional amino acids (also called non-natural amino acids) are any kind of non-oligomeric compounds that contain an amino group and a carboxyl group and that are not conventional amino acids.

[1249] The example of the unconventional amino acid and other building blocks (building block) that are used for building compound of the present invention is identified according to their abbreviation or name shown in Table 4.The structure of some building blocks uses the exemplary reagent (for example, as the unit of carboxylic acid sample) that is used to introduce building blocks into peptide and describes, or these building blocks are shown as residue, and described residue is connected to another structure such as peptide or amino acid completely.Amino acid whose structure is shown as clear and definite amino acid rather than the amino acid residue form that presents after they are implemented in peptide sequence.For the sake of clarity, also show some larger chemical parts that are made up of more than one part.

[1250] Table 4: Abbreviations, names and structures of unnatural amino acids and other building blocks and chemical moieties

[1251]

[1252]

[1253]

[1254]

[1255]

[1256]

[1257]

[1258]

[1259]

[1260]

[1261]

[1262]

[1263]

[1264] As will be appreciated by those of ordinary skill, the amino acid sequence of peptides provided herein is described with typical peptide sequence form.For example, the abbreviation indication amino acid or structural unit of conventional amino acid three letter code or unconventional amino acid code or other structural unit is in the existence of the designated position in peptide sequence.The code of each amino acid or structural unit is connected to the code of the next and / or previous amino acid or structural unit in the sequence by hyphen (usually representing amide bond).

[1265] Where an amino acid contains more than one amino and / or carboxyl group, all orientations of the amino acid are generally possible, but in α-amino acids, utilization of both α-amino and α-carboxyl groups is preferred, otherwise a preferred orientation is explicitly specified.

[1266] For amino acids, in their abbreviations, the first letter indicates the stereochemistry of the C-α-atom, if applicable. For example, an uppercase first letter indicates that the L-form of the amino acid is present in the peptide sequence, while a lowercase first letter indicates that the D-form of the corresponding amino acid is present in the peptide sequence.

[1267] In one embodiment, and as preferably used herein, an aromatic amino acid is any class of amino acids comprising an aryl or heteroaryl group.

[1268] In one embodiment, and as preferably used herein, an aromatic α-amino acid is any kind of α-amino acid comprising an aryl or heteroaryl group.

[1269] In one embodiment, and as preferably used herein, an α-amino acid is an amino acid wherein the amino group and the carboxyl group are substituents of the same carbon atom.

[1270] It will be appreciated by those skilled in the art that whether there is a stereocenter in the compounds disclosed herein, no matter such stereocenter is a part for an amino acid moiety or a part for any other part or group of the application's compound. Therefore, the application includes possible stereoisomers, not only including racemic compounds, but also including independent enantiomers and / or diastereomers. When needing compound as a single enantiomer or diastereomer, it can be synthesized by stereospecificity or obtained by the splitting of final product or any suitable intermediate. The splitting of final product, intermediate or starting material can be achieved by any suitable method known in the art. See, for example, " Stereochemistry of Organic Compounds " (Wiley-Interscience, 1994) by E.L. Eliel, S.H. Wilen and L.N. Mander.

[1271] In the present application, for convenience, the structural formula of a compound represents a certain isomer in some cases, but the present application includes all isomers, such as geometric isomers, optical isomers based on asymmetric carbon, stereoisomers, tautomers, etc.

[1272] Unless otherwise indicated, amino acid sequences are presented herein in N-terminal to C-terminal direction.

[1273] Linear peptides

[1274] Typical linear peptides are usually written from the N-terminus to the C-terminus as follows:

[1275] Z 1 -Xaa1-Xaa2-Xaa3-Xaa4-……Xaan-Z 2

[1276] in

[1277] 1. Xaax is the abbreviation, descriptor or symbol for the amino acid or building block at position x of a particular sequence as shown in Table 4, wherein the linear connection of individual Xaax is indicated by a hyphen,

[1278] 2.Z 1 is the N-terminal group, which can be a chelator or the N-terminal group NT, such as 'H' (hydrogen of the free N-terminal amino group) or a specific terminating carboxylic acid, such as 'Ac' which is an abbreviation for acetic acid, or another chemical group or structural formula of a chemical group connected via a hyphen to the N-terminal amino acid code (Xaa1); and

[1279] 3.Z 2is the C-terminal group, which is typically the C-terminal group CT, such as 'OH' or 'NH2' (as a terminal carboxylic acid or amide), but may also be an amino acid connected to the chelator via an optional linker.

[1280] Branched peptides with side chains modified by specific building blocks or peptides

[1281] A typical linear branched peptide is written from the N-terminus to the C-terminus as follows:

[1282] Z 1 -Xaa1-Xaa2-Xaa3(Z 3 -Xab1-Xab2-…Xabn)-…Xaan-Z 2

[1283] For the description of Xaax, Z 1 and Z 2 , using linear peptides as described in 1-3 above.

[1284] The position of the branch is specified by brackets immediately following the abbreviation Xaax.The branch typically occurs at a lysine (Lys) residue (or analogue), meaning that the branch is attached to the side chain epsilon-amino function of the lysine via an amide bond.

[1285] The bracketed content describes the peptide branch 'Z 3 -Xab1-Xab2-……Xabn' sequence / structure.

[1286] 1. Xabx is an abbreviation, descriptor or symbol for the amino acid or building block at a specific sequence position x of the branch as shown in Table 4, wherein the linear connection of individual Xabx is indicated by a hyphen,

[1287] 2.Z 3 is the N-terminal group of the branch, which is typically a chelator attached to the N-terminal amino acid Xab1 or 'H', which indicates the free amino group of Xab1, and

[1288] 3. The last structural unit of the branch, Xabn, forms an amide bond between the branch and the main chain via its own carboxyl functional group and the side chain amino functional group of the lysine (or similar residue).

[1289] In addition, the content of the brackets can be a chemical group of a specific heteroatom connected to the side chain of the structural unit / amino acid Xaax (e.g., methyl is Me). For the sake of clarity, these residues (e.g., Arg(Me) or Gln(Gu)) are included in Table 4.

[1290] Cyclic peptides

[1291] An exemplary general cyclic peptide, written from the N- to C-terminus direction, is shown below:

[1292] Z 1 -Xaa1-[Xaa2-Xaa3-Xaa4-………Xaan]-Z 2

[1293] Among them, for the description of Xaax, Z 1 and Z 2 , using the description of linear peptides in 1-3 above. Peptide ring features are specified by square brackets.

[1294] 1. The right open square bracket indicates the structural unit at whose side chain the ring begins, and

[1295] 2. The left open square bracket indicates the structural unit at whose side chain the ring is terminated.

[1296] The chemical nature of the connection between these two residues is:

[1297] 1. Typically a disulfide bond where both residues / amino acids are cysteine ​​and therefore contain a sulfhydryl moiety, or 2. a thioacetal linkage where one of the residues is S-methylcysteine ​​and the other is cysteine.

[1298] In addition, cyclic peptides may contain branches at certain positions within their linear sequence. In this case, the expression "branched peptide having side chains modified by a specific structural unit or peptide" is used.

[1299] As a non-limiting example, the structure of DOTA-Cmp-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0492) is depicted below.

[1300]

[1301] in:

[1302] 1. DOTA chelating agent corresponds to Z in general formula (I) 1 .

[1303] 2. Cmp and Thr together form L in formula (I) 1 .

[1304] 3. Aib and Phe correspond to Xaa2 and Xaa3 in the general formula (I), respectively.

[1305] 4. Lys, Arg, Aib and Asn correspond to Xaa5, Xaa6, Xaa7 and Xaa8 in the general formula (I), respectively.

[1306] 5. Tle corresponds to Xaa10 in the general formula (I).

[1307] 6.Thr corresponds to L in general formula (I) 2 .

[1308] 7.NH2 corresponds to Z in the general formula (I) 2 .

[1309] 8. A right open square bracket ('[') adjacent to the N-terminal cysteine ​​in the sequence indicates that the loop begins at that residue.

[1310] 9. A left open square bracket (']') adjacent to the N-terminal cysteine ​​in the sequence indicates that the loop terminates at that residue.

[1311] In one embodiment, the compounds of the invention comprise a chelating agent. Preferably, the chelating agent is part of the compounds of the invention, wherein the chelating agent is directly or indirectly attached to the compounds of the invention, for example, via a linker. Preferred chelating agents are those that form metal chelates, preferably comprising at least one radioactive metal. The at least one radioactive metal is preferably useful or suitable for diagnosis and / or treatment and / or theranostic use, and more preferably useful or suitable for imaging and / or radiotherapy.

[1312] Chelating agents that can be used for and / or are applicable to implementing the present invention (including diagnosis and / or treatment of disease) are generally known to those skilled in the art. A variety of corresponding chelating agents are available, and for example, by the like (Banerjee, et al., Dalton Trans, 2005, 24: 3886) of Banerjee and references therein (Price, et al., ChemSoc Rev, 2014, 43: 260; Wadas, et al., Chem Rev, 2010, 110: 2858) review. Such chelating agents include but are not limited to linear, cyclic, macrocyclic, tetrapyridine, N3S, N2S2 and N4 chelating agents disclosed in US 5,367,080 A, US 5,364,613 A, US 5,021,556 A, US 5,075,099 A and US 5,886,142 A.

[1313] Representative chelators and their derivatives include, but are not limited to, the examples listed in Table 7, including any bifunctional form that can be conjugated to a targeting vector.

[1314] Table 7: Examples of chelating agents and their corresponding chemical names and exemplary references where they are disclosed.

[1315]

[1316]

[1317]

[1318]

[1319]

[1320]

[1321]

[1322]

[1323] a)Price,et al.,Chem Soc Rev,2014,43:260.

[1324] b)Wadas et al.,Curr.Pharm.Des.2007,13(1)

[1325] c)Franchi et al.,Nucl.Med.Biol.2022,114-115,168

[1326] d)Allott et al.,Chem Commun(Camb)2017,53,8529

[1327] e)Cusnir et al.,Int J Mol Sci 2017,18

[1328] f)Demoin,et al.,Nucl Med Biol 2016,43:802

[1329] g)Egorova et al.,Russ.Chem.Rev.2019,88(9),901

[1330] h)Yang et al.,J.Nucl.Med.2022,63(1),5

[1331] i)Grieve et al.,Aust.J.Chem.2022,75,65

[1332] i)Odendaal et al.,Inorg Chem.2011,50(7),3078

[1333] k)Pandya et al.,Bioconjugate Chem.2012,23(3),330

[1334] 1)Gai et al.,Inorg Chem.2016,55(I4),6892

[1335] m)Seemann et al.,ChemMedChem 2015,10(6),1019

[1336] n)Kálmán et al.,Inorg.Chem.2008,47(9),3851

[1337] o)Trayagin et al.,Synlett 2020,31,1291

[1338] p)Woods et al.,Chemistry 2019,25(42),9997

[1339] q)Ramogida et al.,Inorg.Chem.2015,54,2017

[1340] r)Barge et al.,Org.Biomol.Chem.2009,7,3810

[1341] s)Kostelnik et al.,Chem.Rev.2019,119(2),902

[1342] t)Li et al.,Pharmaceutics 2023,15,414

[1343] u)McAuley,et al.,Can.J.Chem.1989,67,1657

[1344] v)Maecke et al.in:PET Chemistry(Springer Berlin Heidelberg)2007,64,215

[1345] w)Mazzi et al.in:Technetium-99m pharmaceuticals(Berlin:Springer)2007,7-58

[1346] x)McDonagh et al.,Inorg.Chem.2021,60,10030

[1347] y)Poty et al.,ChemMedChem 2015,10(9),1475

[1348] z)AlHokbany et al.,EJNMMI Radiopharm Chem.2022,7(19)

[1349] aa) et al.,RSC Adv.2020.10,21329

[1350] bb)Egorova et al.,Molecules 2022,27,3115

[1351] cc)Straathof et al.,Molecules 2021,26,4603

[1352] dd)Yu et al.,J.Inorg.Biochem.2016,154,89

[1353] ee)Lozza et al.,Front.Oncol.2013,3,247

[1354] ff)Heath et al.,Nutrients 2013,5(8),2836

[1355] gg)Wadas et al.,Chem.Rev.2010,110(5),2858

[1356] hh)Stimmel et al.,Bioconjugate Chem.1995,6(2),219

[1357] ii)Yokel et al.,J.Pharm.Sci.2000,89(4),545

[1358] ii)Woodin et al.,Eur.J.Inorg.Chem.2005,4829

[1359] kk)Lima et al.,Inorg.Chem.2014,53(10),5269

[1360] ll)Cai et al.,J.Label Compd.Radiopharm 2014,57,224

[1361] mm)Guo et al.,JHematol Oncol.2016,9,98

[1362] nn)Kanchi et al.,Arab.J.Chem.2014,7(1),1

[1363] oo)Feiner et al.,Cancers 2021,13,4

[1364] pp)Lyczko et al.,Polyhedron 2020,192,114822

[1365] qq)Chang et al.,Dalton Trans.,2013,42,6397

[1366] rr)Serda et al.,PLOS ONE 2014,9(10),e110291

[1367] ss)Ingham et al.,Inorg.Chem.2022,61(24),9119

[1368] tt)McBride et al.,EJNMMI Research 2013,3(36)

[1369] HYNIC, DTPA, EDTA, DOTA, TETA and bisaminobisthiol (BAT)-based chelators are disclosed in US 5,720,934; deferoxamine (DFO) is disclosed in Doulias et al. (Doulias, et al., Free Radic Biol Med, 2003, 35:719); tetrapyridine and N3S, N2S2 and N4 chelators are disclosed in US 5,367,080 A, US 5,364,613 A, US 5,021,556 A, US 5,075,099 A, US 5,886,142 A, all of which are incorporated herein by reference in their entirety. Pfister et al. (Pfister, et al., EJNMMI Res, 2015, 5:74) disclosed 6-amino-6-methylperhydro-1,4-diaza-N,N′,N″,N″-tetraacetic acid (AAZTA); Cusnir et al. (Cusnir, et al., Int J Mol Sci, 2017, 18) disclosed deferiprone, i.e., 1,2-dimethyl-3,4-hydroxypyridone and hexadentate tris(3,4-hydroxypyridone) (THP); Demoin et al. (Demoin, et al., Nucl Med Biol, 2016, 43:802) disclosed chelating agents based on monoamine-monoamide dithiol (MAMA); Thiele et al. (Thiele, et al., Angew Chem Int Ed Macropa and its analogs are disclosed in (Engl, 2017, 56: 14712); 1,4,7,10,13,16-hexaazacyclohexadecane-N,N',N",N"',N"",N""'-hexaacetic acid (HEHA) and PEPA analogs are disclosed in Price and Orvig (Price, et al., Chem Soc Rev, 2014, 43: 260); pycup and analogs are disclosed in Boros et al. (Boros, et al., Mol Pharm, 2014, 11: 617); N,N-bis(2-hydroxybenzyl)ethylenediamine-N,N-diacetic acid (HBED), 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane (TCM), 2-[(carboxymethyl)]-[5-(4-nitrophenyl-1-[4,7,10-tris-(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl]pentan-2-yl)-amino]acetic acid (3p-C-DEPA), CB-TE2A, TE2A, TE1A1P, DiAmSar, 1-N-(4-aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]-eicosane-1,8-diamine (SarAr), NETA, tris(2-mercaptoethyl)-1,4,7-triazacyclononane (TACN-TM), {4-[2-(bis-carboxymethyl-amino)-ethyl]-7-carboxymethyl-[1,4,7]triazacyclononane-1-yl}-acetic acid (NETA), diethylenetriaminepentaacetic acid (DTP), 3-({4,7-bis-[(2-carboxyethyl)-hydroxy-phosphonomethyl]-[1,4,7]triazacyclononane-1-yl}-acetic acid

[0015] 1,4,7,10,13-pentaazacyclopentadecane-N,N',N",N"',N""-pentaacetic acid (PEPA) is disclosed in Price and Orvig (Price, et al.). al., Chem Soc Rev, 2014, 43:260); Allott et al. (Allott, et al., Chem Commun (Camb), 2017, 53:8529) disclosed 1-hydroxy-2-pyridone ligand (HOPO); Tornesello et al. (Tornesello, et al., Molecules, 2017, 22:1282) disclosed [4-carboxymethyl-6-(carboxymethyl-methyl-amino)-6-methyl-[1,4]diazepan-1-yl]-acetic acid (DATA); McAuley 1988 (McAuley, et al., Canadian Journal of Chemistry, 1989, 67:1657) disclosed tetrakis(aminomethyl)methane (TAM) and its analogs; Ma et al. (Ma, et al., Dalton Trans, 2015, 44: 4884) discloses hexadentate tris(3,4-hydroxypyridone) (THP) and its analogs.

[1370] Some of the above chelators are described in the prior art for diagnostic and / or therapeutic use. For example, 2-hydrazinonicotinamide (HYNIC) has been widely used to incorporate 99m Tc and 186,188 Re (Schwartz, et al., Bioconjug Chem, 1991, 2:333; Babich, et al., J Nucl Med, 1993, 34: 1964; Babich, et al., Nucl Med Biol, 1995, 22: 25); DTPA is used Used for complexation 111In, and several modifications are described in the literature (Li, et al., Nucl Med Biol, 2001, 28:145; Brechbiel, et al., Bioconjug Chem, 1991, 2:187); Tweedle et al. (U.S. Patent 4,885,363) describe DOTA-type chelators for radiotherapy applications; Eisenwener et al. (Eisenwener et al., Bioconjug Chem, 2002, 13:530) describe other polyaza macrocycles for chelating trivalent isotopic metals; and N4-chelators (e.g. 99m Tc-N4-chelate) has been used for peptide labeling in the context of minigastrin targeting the CCK-2 receptor (Nock, et al., J Nucl Med, 2005, 46: 1727).

[1371] In one embodiment, the chelating agent is selected from the group comprising, but not limited to, DOTA, DOTAGA, DOTAM, Crown, DOTP, NOTA, NODAGA, NODA-MPAA, HBED, TETA, CB-TE2A, DTPA, CHX-A"-DTPA, DFO, Macropa, HOPO, TRAP, THP, DATA, NOPO, NOTP, PCTA, LSC (or PSC), sarcophagine, FSC, NETA, NE3TA, H4octaa, pycup, HYNIC, NxS4-x (N4, N2S2, N3S), 99m Tc(CO)3-chelators and analogs thereof Preferably, the chelator further comprises one or more functional groups or functionalities capable of being linked to the compounds of the present invention.

[1372] Its chemical structure is as follows:

[1373]

[1374]

[1375] In one embodiment, the chelating agent is selected from the group consisting of DOTA, DOTAGA, NOPO, PCTA, NOTA, NODAGA, NODA-MPAA, HBED, TETA, CB-TE2A, DTPA, DFO, Macropa, Crown, DOTAM, HOPO, TRAP, THP, DATA, NOTP, LSC (or PSC), sarcophagine, FSC, NETA, H4octapa, Pycup, Nx S 4-x (N4,N2S2,N3S), Hynic, 99m Tc(CO)3-chelating agent.

[1376] In another embodiment, the chelating agent is selected from DOTA, DOTAGA, NOPO, PCTA, DOTAM, Macropa, Crown, NOTA, NODAGA, NODA-MPAA, HBED, CB-TE2A, DFO, THP, LSC (or PSC) and N4.

[1377] In another embodiment, the chelating agent is selected from the group consisting of DOTA, DOTAGA, NOPO, PCTA, DOTAM, Macropa, Crown, NOTA, LSC (or PSC), and NODAGA.

[1378] In another embodiment, the chelating agent is selected from the group consisting of DOTA, DOTAM, Macropa, Crown, NOTA, LSC (or PSC), and NODAGA.

[1379] In another embodiment, the chelating agent is DOTA.

[1380] Preferably, the chelating agent further comprises one or more functional groups or functionalities capable of being attached to the compounds of the invention.

[1381] Those skilled in the art will appreciate that chelators may generally be used regardless of whether the compound of the invention is used or suitable for diagnosis or therapy.Such principles are outlined in International Patent Application WO 2009 / 109332 A1.

[1382] Those skilled in the art will further recognize that, unless otherwise stated, the presence of a chelating agent in the compounds of the present invention encompasses the possibility of the chelating agent being complexed with any metal complex partner, i.e., in principle, any metal that can be complexed by a chelating agent. An explicit reference to a chelating agent in the compounds of the present invention or the general term chelating agent in relation to the compounds of the present invention refers to an uncomplexed chelating agent or a chelating agent bound to any metal complex partner, wherein the metal complex partner is any radioactive or non-radioactive metal complex partner. Preferably, the chelating agent-metal complex, i.e., the chelating agent bound to the metal complex partner, is a stable chelating agent-metal complex.

[1383] Non-radioactive chelating agent-metal complexes have several applications, such as for assessing stability or active properties that are difficult to determine. One aspect is that cold variants of the radioactive form of the metal complex partner (e.g., non-radioactive indium complexes as described in the Examples) can serve as substitutes for radioactive compounds. In addition, they are valuable tools for identifying metabolites in vitro or in vivo and for assessing the toxic properties of the compounds of this invention. Additionally, chelating agent-metal complexes can be used for combining determinations utilizing the fluorescent properties of some metal complexes with different ligands (e.g., europium salts).

[1384] Chelators can be synthesized or commercially available with a variety of (possibly activated) groups for conjugation to peptides or amino acids.

[1385] Direct conjugation of the chelating agent to the amino-nitrogen of the corresponding compound of the invention is possible for a chelating agent selected from the group consisting of DTPA, DOTA, DOTAGA, NOTA, NODAGA, NODA-MPAA, HBED, TETA, CB-TE2A, DFO, DATA, sarcophagine and N4, preferably DTPA, DOTA, DOTAGA, NOTA, NODAGA, NODA-MPAA, CB-TE2A and N4. The preferred linkage in this regard is an amide bond.

[1386] Direct conjugation of isothiocyanate functionalized chelators to the amino-nitrogen of the compounds of the present invention is possible for chelators selected from the group consisting of DOTA, DOTAGA, NOTA, NODAGA, DTPA, CHX-A"-DTPA, DFO and THP, preferably DOTA, DOTAGA, NOTA, NODAGA, DTPA and CHX-A"-DTPA. The preferred linkage in this regard is a thiourea bond.

[1387] Chelating agent functional groups that are preferred precursors for direct conjugation of chelating agents to amino-nitrogen are known to those skilled in the art and include, but are not limited to, carboxylic acids, activated carboxylic acids, for example activated esters such as NHS-esters, pentafluorophenol-esters, HOBt-esters, HOAt-esters and isothiocyanates.

[1388] Chelating agent functional groups that are preferred precursors for direct conjugation of chelating agents to carboxyl groups are known to those skilled in the art and include, but are not limited to, alkylamino and arylamino nitrogens. Corresponding chelating agent reagents are commercially available for some chelating agents, such as DOTA with alkylamino or arylamino nitrogens.

[1389] Chelating agent functional groups that are preferred precursors for direct conjugation of chelators to thiols are known to those skilled in the art and include, but are not limited to, the nitrogen of maleimide. Corresponding chelating agent reagents are commercially available for some chelators, for example, for DOTA with a maleimide nitrogen.

[1390] Functional groups of chelating agents that are preferred precursors for direct conjugation of chelating agents to azide groups are known to those skilled in the art and include, but are not limited to, acyclic alkynes and cyclic alkynes. Corresponding chelating agents are commercially available for some chelating agents, for example, DOTA with a propargyl or butynyl group.

[1391] Functional groups of chelating agents that are preferred precursors for direct conjugation of chelating agents to alkynyl groups are known to those skilled in the art and include, but are not limited to, alkyl and aryl azines. Corresponding chelating agents are commercially available for some chelating agents, for example, for DOTA with an azidopropyl group.

[1392] It will be understood by those skilled in the art that the radionuclide to be attached to the compounds of the present application is selected taking into account the disease to be treated and / or the disease to be diagnosed and / or the particularities of the patient and patient group to be treated and diagnosed, respectively.

[1393] In this application, radioactive nuclides are also referred to as radionuclides. Radioactive decay is the process by which the nucleus of an unstable atom loses energy by emitting ionizing particles (ionizing radiation). There are different types of radioactive decay. When an atom with one type of nucleus (called the parent radionuclide) transforms into an atom with a nucleus in a different state, or into a different nucleus containing a different number of protons and neutrons, decay or energy loss occurs. Any of these products is named a daughter nuclide. In some decays, the parent and daughter are different chemical elements, so the decay process results in nuclear transmutation (the production of atoms of new elements). For example, radioactive decay can be alpha decay, beta decay, and gamma decay. Alpha decay occurs when a nucleus ejects an alpha particle (helium nucleus). This is the most common process for emitting nucleons, but in rarer types of decay, a nucleus can eject protons or specific nuclei of other elements (in a process called cluster decay). When a nucleus emits electrons (beta decay) in the process of changing protons into neutrons or other ways, - - decay) or positron (β +Beta decay occurs when a nucleus is exposed to a combination of a proton-like decay (β-decay) and a type of neutrino. In contrast, there are radioactive decay processes that do not result in transmutation. The energy of the excited nucleus can be emitted as gamma rays in the form of gamma decay, or used to eject orbital electrons by interacting with the excited nucleus in a process called internal conversion, or used to absorb internal atomic electrons from electron shells, where the change of a nuclear proton to a neutron causes the emission of an electron neutrino in a process called electron capture (EC), or can be emitted without changing the number of its protons and neutrons in a process called isomerization transition (IT). Another form of radioactive decay, spontaneous fission (SF), is found only in very heavy chemical elements and results in the spontaneous decomposition of an atomic nucleus into smaller nuclei and several isolated nuclear particles.

[1394] In one embodiment, compounds comprising radionuclides are described herein. Typically, the type of radionuclide used in therapeutic radiopharmaceuticals can be customized for a specific type of cancer and the type of targeting moiety. Radionuclides that undergo alpha decay produce particles consisting of two neutrons and two protons, and radionuclides that undergo beta decay emit high-energy electrons from their nuclei. Some radionuclides can also emit Auger electrons. In some embodiments, conjugates include radionuclides that emit alpha particles. Compared to gamma and beta radiation, which can cause single-strand breaks by indirect DNA damage, alpha radiation can cause direct, irreparable double-strand DNA breaks. The range of these particles in tissues and the half-life of the radionuclide can also be considered when designing radiopharmaceutical conjugates.

[1395] Radionuclides as α-emitters can destroy tumors while causing very limited damage to surrounding healthy tissues due to the short penetration depth of α particles. Compared with other radionuclide therapies, their high linear energy transfer (LET) gives them improved relative biological effectiveness (RBE). In addition, when the specific tumor cells in vivo of the radionuclide target of α-emitting α-are very effective in destroying metastatic tumors, which are difficult to treat by currently used technologies (de Kruijff et al, Pharmaceuticals, 2015, 8:, 321-336).

[1396] In an embodiment of the present application, radionuclides can be used to label the compounds of the present application.

[1397] In one embodiment of the present application, the radionuclide is suitable for complexing with a chelating agent to produce a radionuclide chelate complex.

[1398] In another embodiment, one or more atoms of the compounds of the present invention are non-natural isotopic compositions, for example, these atoms are radionuclides; for example, radionuclides of carbon, oxygen, nitrogen, sulfur, phosphorus and halogens. These radioactive atoms are typically part of amino acids, in some cases halogen-containing amino acids and / or building blocks, and in some cases are halogenated building blocks of each compound of the present invention.

[1399] In one embodiment of the present application, the radionuclide has a half-life that allows for diagnostic and / or therapeutic medical use. Specifically, the half-life is between 1 minute and 100 days.

[1400] In embodiments of the present application, the radionuclide has a decay energy that allows for diagnostic and / or therapeutic medical use. Specifically, for gamma-emitting isotopes, the decay energy is between 0.004 MeV and 10 MeV, for example, between 0.05 MeV and 4 MeV, for diagnostic use. For positron-emitting isotopes, the decay energy is between 0.6 and 13.2 MeV, for example, between 1 and 6 MeV, for diagnostic use. For particle-emitting isotopes, the decay energy is between 0.039 and 10 MeV, for example, between 0.4 and 6.5 MeV, for therapeutic use.

[1401] In one embodiment of the present invention, the radionuclides are produced industrially for medical use. In particular, the radionuclides are available at GMP quality levels.

[1402] In one embodiment of the present application, the daughter nuclides after radioactive decay of the radionuclide are compatible with diagnostic and / or therapeutic medical uses. In addition, the daughter nuclides remain stable or undergo further decay in a manner that does not interfere with or even support the diagnostic and / or therapeutic medical uses. Representative radionuclides that can be used in conjunction with the present application are well known to those skilled in the art and include, but are not limited to, the following:

[1403] 11 C, 13 N, 18 F, 24 Na, 28 Mg, 31 Si, 32 P, 33 p, 38 S, 34m Cl, 38 Cl, 39 Cl, 37 Ar, 41 Ar, 44 Ar, 42 K, 43 K, 44 K,45 K, 47 Ca, 43 sc 44 sc 44m sc 47 sc 48 sc 49 sc 45 tea 47 V, 48 V, 48 Cr, 49 Cr. 51 Cr, 51 Mn, 52 Mn, 52m Mn, 56 Mn, 52 Fe, 59 Fe, 55 Co., 61 Co., 62m Co., 56 No, 57 No, 65 No, 66 No, 60 Cu, 61 Cu, 64 Cu, 67 Cu, 62 Zn, 63 Zn, 69 Zn, 69m Zn, 71m Zn, 72 Zn, 65 No, 66 No, 67 No, 68 No, 70 No, 72 No, 73 No, 66 Yes, 67 Yes, 69 Yes, 71 Yes, 75 Yes, 77 Yes, 78 Yes, 69 As 70 As 71 As, 72 As 74 As 76 As 77 As 78 As 70 Se, 72 Se, 73 Se, 73mSe, 81 Se, 81m Se, 83 Se, 74 Br, 74m Br, 75 Br, 76 Br, 77 Br, 80 Br, 80m Br, 82 Br, 83 Br, 84 Br, 74 Kr, 76 Kr, 77 Kr, 79 Kr, 85 Kr, 87 Kr, 88 Kr, 78 Rb, 79 Rb, 81 Rb, 82 Rb, 84 Rb, 84m Rb, 86 Rb, 88 Rb, 89 Rb, 80 Sr, 81 Sr, 82 Sr, 83 Sr, 85m Sr, 87 Sr, 91 Sr, 92 Sr, 84 Y, 85 Y, 85m Y, 86 Y, 86m Y, 87 Y, 87m Y, 90 Y, 90m Y, 91m Y, 92 Y, 93 Y, 94 Y, 95 Y, 86 Zr, 87 Zr, 89 Zr, 97 Zr, 88 Nb, 89 Nb, 89m Nb, 90 Nb, 92 Nb, 95 Nb, 95m Nb, 96 Nb,97 No, 98m No, 101 My, 102 My, 90 My, 91M oh, 93m My, 99 My, 101 Tc, 104 Tc, 93 Tc, 93m Tc, 94 Tc, 94m Tc, 95 Tc, 96 Tc, 99 mTc, 103 Yes, 105 Yes, 94 Yes, 95 Yes, 97 Yes, 100 Oh, 101 Mr., 105 Oh, 106m Rh, 1 07 Oh, 97 Oh, 97m Oh, 99 Oh, 99m Oh, 100 Pd, 101 Pd, 103 Pd, 109 Pd, 111 Pd, 111m Pd, 112 Pd, 98 Pd, 99 Pd, 101 At, 103 At, 104 At, 104 Yes, 105 At, 106 At, 106m At, 111 At, 112 At, 113 At, 115 At, 104 Cd, 105 Cd, 107 Cd, 111 Cd, 115 Cd, 115m Cd, 117 Cd, 117m Cd, 118 Cd, 107 In, 108m In,109 In, 110 In, 110m In, 111 In, 112 In, 113 In, 114m In, 115m In, 116m In, 117 In, 117m In, 119m In, 108 Sn, 109 Sn, 110 Sn, 111 Sn, 117 Sn, 121 Sn, 123m Sn, 125 Sn, 127 Sn, 128 Sn, 115 Sb, 116 Sb, 116m Sb, 117 Sb, 118m Sb, 119 Sb, 120 Sb, 120m Sb, 122 Sb, 126 Sb, 126m Sb, 127 Sb, 128 Sb, 128m Sb, 129 Sb, 129m Sb, 130 Sb, 131 Sb, 114 Te, 116 Te, 117 Te, 118 Te, 119 Te, 119m Te, 121 Te, 127 Te, 129 Te, 129m Te, 131 Te, 131m Te, 132 Te, 133 Te, 133m Te, 134 Te, 118 I, 119 I, 120 I, 120m I, 121 I, 123 I, 124 I,126 I, 128 I, 130 I, 131 I, 132 I, 132m I, 133 I, 134 I, 135 I, 120 Xe, 121 Xe, 122 Xe, 123 Xe, 125 Xe, 127 Xe, 133 Xe, 133m Xe, 135 Xe, 135m Xe, 138 Xe, 125 Cs, 127 Cs, 129 Cs, 130 Cs, 131 Cs, 132 Cs, 134 Cs, 135 Cs, 136 Cs, 138 Cs, 124 Well, 126 Well, 127 Well, 128 Well, 129 Well, 129m Well, 131 Well, 131m Well, 133 Well, 135 Well, 139 Well, 140 Well, 141 Well, 142 Well, 129 At, 131 At, 132 At, 133 At, 135 At, 140 At, 141 At, 142 At, 143 At, 130 What, 132 What, 133 What, 133 What, 134 What, 135 What, 137 What, 137m What, 141 What, 143 What,146 Ce, 134 Pr, 134m Pr, 136 Pr, 137 Pr, 138m Pr, 139 Pr, 142 Pr, 143 Pr, 144 Pr, 145 Pr, 146 Pr, 147 Pr, 135 And 136 And 137 And 138 And 139 And 139m And 140 And 141 And 147 And 149 And 151 And 152 And 141 Pm, 148 Pm, 148m Pm, 149 Pm, 150 Pm, 151 Pm, 140 Sm, 141 Sm, 141 mSm, 142 Sm, 153 Sm, 155 Sm, 156 Sm, 145 I, 146 I, 147 I, 150 I, 152m I, 154 I, 156 I, 157 I, 158 I, 159 I, 145 Gd, 146 Gd, 147 Gd, 149 Gd, 159 Gd, 147 Also, 148 Also, 149 Also, 150 Also, 151 Also, 152 Also, 153 Also, 154 Also, 154 mTb,155 Tb, 156 Tb, 156m Tb, 161 Tb, 163 Tb, 151 Of, 152 Of, 153 Of, 155 Of, 157 Of, 165 Of, 166 Of, 154 Ho 155 Ho 156 Ho 157 Ho 158 mHo, 159 Ho 161 Ho 162 Ho 162m Ho 164 Ho 164m Ho 166 Ho 167 Ho 156 On, 157 On, 158 On, 159 On, 160 On, 161 On, 163 On, 165 On, 169 On, 171 On, 172 On, 161 tm, 162 tm, 163 tm, 165 tm, 166 tm, 167 tm, 172 tm, 173 tm, 175 tm, 162 Yb, 163 Yb, 164 Yb, 166 Yb, 167 Yb, 169 Yb, 175 Yb, 177 Yb, 178 Yb, 167 Lu 169 Lu 170 Lu 171 Lu 172 Lu 176m Lu 177 Lu 178 Lu178m Hello, 179 Hello, 168 Hf, 170 Hf, 173 Hf, 177m Hf, 179m Hf, 180m Hf, 181 Hf, 182m Hf, 183 Hf, 184 Hf, 172 Yes, 173 Yes, 174 Yes, 175 Yes, 176 Yes, 177 Yes, 178 Yes, 180 Yes, 182 Yes, 183 Yes, 184 Yes, 185 Yes, 186 Yes, 174 W, 175 W, 177 W, 178 W, 179 W, 187 W, 190 W, 177 Yes, 178 Yes, 179 Yes, 181 Yes, 182 Yes, 182m Yes, 184 Yes, 186 Yes, 188 Yes, 188m Yes, 189 Yes, 190m Yes, 180 Because, 181 Because, 182 Because, 183 Because, 183m Because, 191 Because, 193 Because, 196 Because, 182 Yes, 183 Yes, 184 Yes, 185 Yes, 186 Yes, 186m Yes, 187 Yes, 188 Yes, 189 Yes, 190 Yes, 194 Yes,195 Ir, 195m Ir, 196m Ir, 184 Pt, 186 Pt, 187 Pt, 188 Pt, 189 Pt, 191 Pt, 195 Pt, 197 Pt, 197m Pt, 199 Pt, 200 Pt, 202 Pt, 186 At, 190 At, 191 At, 192 At, 193 At, 194 At, 196 At, 196m At, 198 At, 198m At, 199 At, 200 At, 200m At, 190 Hg, 191 Hg, 192 Hg, 193 Hg, 195 Hg, 195m Hg, 197 Hg, 197m Hg, 199 Hg, 203 Hg, 194 Tl, 194m Tl, 195 Tl, 196 Tl, 196m Tl, 197 Tl, 198 Tl, 198m Tl, 199 Tl, 200 Tl, 201 Tl, 202 Tl, 194 Pb, 195 Pb, 196 Pb, 197m Pb, 198 Pb, 199 Pb, 199m Pb, 200 Pb, 201 Pb, 202m Pb, 203 Pb, 204 Pb, 209Pb, 211 Pb, 212 Pb, 214 Pb, 200 Bi, 200m Bi, 201 Bi, 202 Bi, 203 Bi, 204 Bi, 205 Bi, 206 Bi, 210 Bi, 212 Bi, 212m Bi, 213 Bi, 214 Bi, 200 Night, 201 Night, 202 Night, 203 Night, 204 Q o , 205 Q o , 206 Q o , 207 Q o , 205 At, 206 At, 207 At, 208 At, 209 At, 210 At, 211 At, 208 Rn, 209 Rn, 210 Rn, 211 Rn, 212 Rn, 221 Rn, 222 Rn, 223 Rn, 212 Fr. 222 Fr. 223 Fr. 223 Ra, 224 Ra, 225 Ra, 227 Ra, 230 Ra, 224 And 225 And 226 And 228 And 229 And 226 Th, 227 Th, 231 Th, 233 Th, 234 Th, 236 Th, 227 pa,228 Pa, 229 pa, 230 pa, 232 Pa, 233 Pa, 234 Pa, 235 Pa, 229 U, 230 U, 231 U, 237 U, 239 U, 240 U, 242 U, 231 Np, 232 Np, 233 Np, 234 Np, 236m Np, 238 Np, 239 Np, 240 Np, 241 Np, 232 Pu, 235 Pu, 237 Pu, 243 Pu, 245 Pu, 246 Pu, 235 Am, 237 Am, 238 Am, 239 Am, 240 Am, 242 Am, 244 Am, 244 mAm, 245 Am, 246 Am, 246m Am, 247 Am, 239 Cm, 240 Cm, 241 Cm, 251 Cm, 245 Bk, 246 Bk, 248 Bk, 250 Bk, 251 Bk, 244 Cf, 245 Cf, 246 Cf, 247 Cf, 253 Cf, 255 Cf, 249 Es, 250 Es, 250 mEs, 251 Es, 253 Es, 254m Es, 255 Es,256m Es, 250 Fm, 251 Fm, 252 Fm, 254 Fm, 255 Fm, 255 Md, 256 Md, 257 Md, 259 No. Their properties are described in more detail in, for example, Nuclear Data Sheets (Elsevier, Amsterdam, NL).

[1404] In embodiments of the present application, the radionuclide is used for diagnosis. In some embodiments, the radioisotope is selected from the group including but not limited to the following: 43 Sc, 44 Sc, 51 Mn, 52 Mn, 64 Cu, 67 Ga, 68 Ga, 86 Y. 89 Zr, 94m Tc, 99m Tc, 111 In, 152 Tb, 155 Tb, 177 Lu, 201 Tl, 203 Pb, 18 F. 76 Br, 77 Br, 123 I. 124 I and 125 1. In some embodiments, the radionuclide is selected from 18 F. 43 Sc, 44 Sc, 64 Cu, 67 Ga, 68 Ga, 86 Y. 89 Zr, 99 mTc, 111 In, 152 Tb, 155 Tb and 203 In some embodiments, the radionuclide is selected from 18 F. 64 Cu, 68 Ga and 111 In one embodiment of the present application, the radionuclide is 18 F, where18 F forms a covalent bond with aluminum, and aluminum forms a metal complex with the chelating agent. 18 Methods and compositions for F labeling are disclosed, for example, in WO 2012 / 082618. However, those skilled in the art will also recognize that the use of such radionuclides when conjugated to the compounds of the present application is not limited to diagnostic purposes, but also encompasses their use in therapy and theranostics.

[1405] In embodiments of the present application, radionuclides are used for treatment. In some embodiments, the radioisotope is selected from 47 Sc, 67 Cu, 89 Sr. 90 Y. 111 In, 153 Sm, 149 Tb, 161 Tb, 177 Lu, 186 Re、 188 Re、 212 Pb, 212 Bi, 213 Bi, 223 Ra, 224 Ra, 225 Ac, 226 Th, 227 Th, 131 I and 211 In some embodiments, the radioisotope is selected from 47 Sc, 67 Cu, 90 Y. 161 Tb, 177 Lu, 188 Re、 212 Pb, 212 Bi, 213 Bi, 225 Ac and 227 In some embodiments, the radionuclide is selected from 90 Y. 161 Tb, 177 Lu, 212 Pb, 225 Ac and 227 However, those skilled in the art will also recognize that the use of such radionuclides when conjugated to the compounds of the present application is not limited to therapeutic purposes, but encompasses their use in diagnosis and theranostics.

[1406] In one embodiment, the compound of the present invention and the disclosure comprises a nuclide combined with a chelating agent (preferred coordination combination) respectively, thereby forming a part for the compound. Those skilled in the art will recognize and understand that the coordination geometry of this complex of nuclide and chelating agent can change. The embodiment of the structure, coordination geometry and total complex charge of various chelate complexes is shown in Table 8.

[1407] Table 8: Selected chelate complexes, their structure, coordination geometry and overall complex charge (coordinate bonds between metal centre and ligand are shown as dashed lines).

[1408]

[1409]

[1410]

[1411]

[1412] a)Wadas et al.,Chem.Rev.2010,110,2858

[1413] b)Aime et al.,Inorg.Chim.Acta 1996,246,423

[1414] c) The ligand DOTA acts as an octadentate ligand. To saturate the coordination region of the metal center, an additional (monodentate) ligand occupies the ninth coordination side. In aqueous solution, the additional ligand is typically a water molecule, but can vary depending on the chemical composition of the environment. For example, the adjacent structure shows a water molecule as an additional ligand.

[1415] d)Shiells et al.,Dalton Trans.2011,40,11451

[1416] e)Grieve et al.,Aust.J.Chem.2022,75,65

[1417] f)Liu et al.,Inorg.Chem.2003,42,8831

[1418] g) DOTAM's Pb has been published 2+ Two crystal structures of the complex. Both structures show eight donor atoms encapsulating the ion but differ in the presence or absence of Pb 2+ Water molecules with weak ionic interactions (Grieve et al., Aust. J. Chem. 2022, 75, 65).

[1419] h)Archibald et al.,EJNMMI radiopharm.chem.2021,6:30

[1420] In one embodiment, the compounds of the present application exist as pharmaceutically acceptable salts.

[1421] In certain embodiments, a "pharmaceutically acceptable salt" of a compound of the present invention is an acid salt or a basic salt that is generally considered in the art to be suitable for use in contact with human or animal tissues without excessive toxicity or carcinogenicity, and, for example, without irritation, allergic reactions, or other problems or complications. Such salts include inorganic and organic acid salts of basic groups such as amines, and alkali or organic salts of acidic groups such as carboxylic acids. The compounds of the present invention are capable of forming internal salts, which are also pharmaceutically acceptable salts.

[1422] Suitable pharmaceutically acceptable salts include, but are not limited to, salts of acids such as hydrochloric acid, phosphoric acid, hydrobromic acid, malic acid, glycolic acid, fumaric acid, sulfuric acid, sulfamic acid, sulfanilic acid, formic acid, toluenesulfonic acid, methanesulfonic acid, benzenesulfonic acid, ethanedisulfonic acid, 2-hydroxyethylsulfonic acid, nitric acid, benzoic acid, 2-acetoxybenzoic acid, citric acid, tartaric acid, lactic acid, stearic acid, salicylic acid, glutamic acid, ascorbic acid, pamoic acid, succinic acid, fumaric acid, maleic acid, propionic acid, hydroxymaleic acid, hydroiodic acid, phenylacetic acid, alkanoic acids (e.g., acetic acid), HOOC-(CH2) n -COOH (wherein n is any integer from 0 to 4, i.e., 0, 1, 2, 3, or 4). Similarly, pharmaceutically acceptable cations include, but are not limited to, sodium, potassium, calcium, aluminum, lithium, and ammonium. Those of ordinary skill in the art will recognize other pharmaceutically acceptable salts of the compounds provided herein. Typically, pharmaceutically acceptable acid salts or base salts can be synthesized from a parent compound containing a basic or acidic moiety by any conventional chemical method. In short, such salts can be prepared by reacting the free acid or base form of these compounds with a stoichiometric amount of a suitable base or acid in water or in an organic solvent or in a mixture of the two. Typically, non-aqueous media such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferably used.

[1423] In one embodiment, the compounds of the present application exist as pharmaceutically acceptable solvates.

[1424] In certain embodiments, a "pharmaceutically acceptable solvate" of a compound of the present application is a solvate of a compound of the present application formed by the association of one or more solvent molecules with one or more molecules of the compound of the present application. In some embodiments, the solvent is a solvent generally recognized in the art as suitable for use in contact with human or animal tissues without excessive toxicity or carcinogenicity and, for example, without irritation, allergic reaction, or other problems or complications. Such solvents include organic solvents, such as alcohols, ethers, esters, and amines.

[1425] In one embodiment, the compounds of the present application exist as hydrates, preferably pharmaceutically acceptable hydrates.

[1426] In certain embodiments, a "hydrate" of a compound of the present invention is formed by the association of one or more water molecules with one or more molecules of the compound of the present invention. Such hydrates include, but are not limited to, hemihydrates, monohydrates, dihydrates, trihydrates, and tetrahydrates. Regardless of the hydrate composition, all hydrates are generally considered pharmaceutically acceptable.

[1427] The compounds of the present application have high binding affinity for PSMA. Due to this high binding affinity, the compounds of the present application are effective, useful, and / or suitable as targeting agents, where the target is PSMA and / or cells and / or tissues expressing PSMA. With respect to cells and tissues targeted by the compounds of the present application, any cells and tissues expressing PSMA are or can be targeted.

[1428] Within this application, the compounds of the present application are used or used in a method for treating a disease as disclosed herein. In certain embodiments, such methods for treating a disease as disclosed herein include the step of administering a therapeutically effective amount of a compound of the present application to a subject in need thereof. The methods include, but are not limited to, curative or adjuvant cancer treatments. It is used as a palliative treatment, where a cure is not possible and the goal is local disease control or symptom relief, or as a therapeutic treatment, where the treatment has a survival benefit and it can be curative.

[1429] The methods for treating diseases as disclosed herein include treating diseases disclosed herein, including tumors and cancers, and can be used as primary therapy or as second-line, third-line, fourth-line or last-line therapy. Combining the compounds of the present application with other therapeutic methods is also within the scope of the present application. It is well known to those skilled in the art that the precise treatment intent includes curative, adjuvant, neoadjuvant, therapeutic or palliative treatment intent, which will depend on the tumor type, location and stage, and the overall health of the patient.

[1430] In one embodiment of the present application, the disease is selected from prostate tumors, metastatic prostate tumors, lung tumors, kidney tumors, glioblastomas, pancreatic tumors, bladder tumors, sarcomas, melanomas, breast tumors, colon tumors, pheochromocytomas, esophageal tumors, stomach tumors, carcinomas, squamous cell carcinomas (e.g., cervical, eyelid, conjunctival, vaginal, lung, oral, skin, bladder, tongue, larynx, and esophagus) and adenocarcinomas (e.g., prostate, small intestine, endometrium, cervical, large intestine, lung, pancreas, esophagus, rectum, uterus, stomach, breast, and ovarian cancer), prostate cancer (e.g., metastatic castration-resistant prostate cancer), kidney cancer (e.g., clear cell carcinoma), head cancer, Neck cancer, head and neck cancer, lung cancer (e.g., non-small cell lung cancer), salivary gland cancer, breast cancer, colorectal cancer, esophageal cancer, stomach cancer, liver cancer (e.g., hepatocellular carcinoma), thyroid cancer, glioblastoma, glioma, gallbladder cancer, laryngeal cancer, leukemia / lymphoma, uterine cancer, skin cancer (e.g., melanoma), endocrine cancer, sarcoma, urethral cancer, pancreatic cancer, gastrointestinal cancer, ovarian cancer, cervical cancer, endometrial cancer, fallopian tube cancer, primary peritoneal cancer, blood cancer (e.g., diffuse large B-cell lymphoma, Hodgkin lymphoma, non-Hodgkin lymphoma, follicular lymphoma, acute myeloid leukemia, or multiple myeloma), cancer of unknown primary site, adenoma, and tumor neovascularization.

[1431] In some embodiments, subjects treated with the compounds disclosed herein can be treated in combination with other non-surgical anti-proliferative (e.g., anti-cancer) drug therapies. In some embodiments, the compound can be administered in combination with an anti-cancer compound such as a cell inhibitory compound. A cell inhibitory compound is a compound (e.g., a small molecule, nucleic acid, or protein) that inhibits cell growth and / or proliferation. In some embodiments, the cell inhibitory compound is directed against malignant cells of a tumor. In some embodiments, the cell inhibitory compound is a compound that inhibits the growth and / or proliferation of vascular smooth muscle cells or fibroblasts.

[1432] In some embodiments, the compounds described herein are used or are used in combination with chemotherapeutic agents, such as DNA damaging chemotherapeutic agents. Non-limiting examples of DNA damaging chemotherapeutic agents include topoisomerase I inhibitors, topoisomerase II inhibitors; alkylating agents; DNA intercalators; DNA intercalators and free radical generators such as bleomycin; and nucleoside mimetics.

[1433] In some embodiments, the compounds described herein can be administered alone or in combination with one or more additional therapeutic agents. For example, a combination therapy may include a composition comprising a conjugate as described herein, co-formulated and / or co-administered with one or more additional therapeutic agents, such as one or more anticancer agents, such as cytotoxic agents or cytostatics, immune checkpoint inhibitors, hormone therapy, vaccines, and / or immunotherapy. In some embodiments, additional therapeutic agents may be selected from cell cycle inhibitors, CDK inhibitors, radiosensitizers, therapeutic agents that upregulate PSMA expression, anti-angiogenic agents, other drugs that reduce hypoxia to increase radiosensitivity, and / or renal protectants. In some embodiments, the conjugate is administered in combination with other therapeutic treatments, including surgery, cryosurgery, and / or chemotherapy. This combination therapy can advantageously utilize lower doses of administered therapeutic agents, thereby avoiding possible toxicity or complications associated with various monotherapies.

[1434] Suitable antiproliferative or cytostatic compounds for use in combination with the compounds disclosed herein include anticancer drugs. Many anticancer drugs that can be used are well known, including but not limited to: acivicin; aclarubicin; acodazole hydrochloride; aclonine; adolesin; aldesleukin; hexamethylmelamine; ambomycin; ametanthrone acetate; aminoglutethimide; amsacrine; anastrozole; anthramycin; asparaginase; trilin; azacitidine; azaribine; azatepa; azomycin; batimastat; benzotepa; bicalutamide; bisantrene hydrochloride; binefad dimesylate; bisezole; bleomycin; bleomycin sulfate; brequinar sodium; bropiridone; bryostatin-1; busulfan; actinomycin; carlosterone; caracetamide; carbetimer; carboplatin; carmustine; carrubicin hydrochloride; carzelesin; cedifingol; celecoxib ; chlorambucil; cyromycin; cisplatin; cladribine; clinapoxetine mesylate; cyclophosphamide; cytarabine; dacarbazine; dactinomycin; daunorubicin; daunorubicin hydrochloride; decitabine; dextromaplatin; dezaguanine; dezaguanine mesylate; diazaquinone; docetaxel; doxorubicin; doxorubicin hydrochloride; doxorubicin glucuronide; cyanomorpholinodoxorubicin; 2-pyrrolidino-doxorubicin (2P-DOX), droloxifene; droloxifene citrate; drolostanone propionate; dazomicin; edatrexate; eflornithine hydrochloride; elsamitrucin; enloplatin; enproamide; epiripridine; epirubicin hydrochloride; epirubicin glucuronide; erbulazole; esorubicin hydrochloride; estramustine; estramustine sodium phosphate; etanercept azole; etoposide; etoposide phosphate; etoposide glucuronide; etopoline; fadrozole hydrochloride; fazarabine; fenretinide; floxuridine (FUdR); 3′,5′-O-dioleoyl-FudR (FUdR-dO); fludarabine; fludarabine phosphate; fluorouracil; flucitabine; flutamide; fluoxymesterone; fosquam; fostramoxine sodium; gemcitabine; gemcitabine hydrochloride; hydroxyurea; hydroxyprogesterone caproate; idarubicin; idarubicin hydrochloride; ifosfamide; imofosine; interferon α-2a; interferon α-2b; interferon α-n1; interferon α-n3; interferon β-Ia; interferon γ-Ib; iproplatin; irinotecan hydrochloride; L-asparaginase; acetate Lanreotide; Letrozole; Leucovorin; Leuprorelin acetate; Lirazol hydrochloride; Lometrexol sodium; Lomustine; Loxantrone hydrochloride; Masoprodol; Maytansine; Nitrogen mustard; Nitrogen mustard hydrochloride; Medroxyprogesterone acetate; Megestrol acetate; Melengesterone acetate; Melphalan; Menogarib; Mercaptopurine; 6-Mercaptopurine; Methotrexate; Methotrexate sodium; Metoprine; Metodepa; Mithracin; Mibutalamide; Mitoxantrone; Mitocromin; Mitogellin; Mitomasin; Mitospe; Mitotane; Mitoxantrone; Mitoxantrone hydrochloride; Mycophenolic acid; Niraparib; Nocodazole; Nogamycin; Olaparib; Omaplatin; Oxisulam; Paclitaxel; Pegaspargase; Pelimycin;Pentamustine; Peplomycin Sulfate; Perfosfamide; Pipobroman phenylbutyrate; Piposulfan; Piroxantrone Hydrochloride; Prilimycin; Promestane; Porfimer Sodium; Porfimer; Prednimustine; Prednisone; Procarbazine; Procarbazine Hydrochloride; PSI-341, Puromycin; Puromycin Hydrochloride; Pyrazolopyridamole; Lipoadenosine; Roglulimide; Rucaparib; Safingol; Safingol Hydrochloride; Semustine; Semustine-Streptozotocin; Simtrazine; Spardronate Sodium Sodium); sparmycin; spirogermanium hydrochloride; spiromustine; spiroplatin; streptozotocin; streptozotocin; sulfonyl urea; talazoparib; talithromycin; paclitaxel; taxotere; tecogalan sodium; tegafur; tiloxantrone hydrochloride; temoporfin; teniposide; tiroxilon; testolactone; thiamidine; thioguanine; thiotepa; thiazofurine; tirapazamine; topotecan; topotecan hydrochloride; toremifene citrate; triptolan acetate; triciribine phosphate; trimetrexate; Trimetrexate glucuronate; tobuclozole hydrochloride; uracil mustard; uredepa; vapreotide; velaparib; Velcade; verteporfin; vinblastine; vinblastine sulfate; vincristine; vincristine sulfate; vindesine; vindesine sulfate; vinpitidine sulfate; vinsodiol sulfate; vinblastine sulfate; vinorelbine; vinorelbine tartrate; vinprodine sulfate; vinblastine sulfate; vorozole; zenaplatin; ninstatin; and zorubicin hydrochloride.

[1435] Other anticancer drugs include, but are not limited to, 20-epi-1,25-dihydroxyvitamin D3; 5-ethynyluracil; abiraterone; acylfulvene; adecypenol; adolesin; ALL-TK antagonists; amustine; amidox; amifostine; aminolevulinic acid; amrubicin; anagrelide; andrographolide; angiogenesis inhibitors; antagonist D; antagonist G; anrelix; anti-dorsal morphogenetic protein-1; antiestrogens; antineoplastons; antisense oligonucleotides; aphidicolin glycinate; apoptosis gene regulators; apoptosis regulators; apurinic nucleic acids; ara-CDP-DL-PTBA; arginine deaminase; asulacrine; atamestane; amustine; axinastatin 1; axinastatin 2; axinastatin 3; azasetron; azatoxin; diazotyrosine; baccatin III derivatives; balanol; batimastat; BCR / ABL antagonists; benzochlorins; benzoylstaurosporine; β-lactam derivatives; β-alethine; betaclamycin B; betulinic acid; bFGF inhibitors; bisaziridinylspermine; bifenafide; bistratene A; bortezomib; breflate; budothiazine; buthionine sulfate imide; calicheamicin; calcipotriol; calphostin C; camptothecin derivatives; canarypox IL-2; capecitabine; carboxamide aminotriazole; carboxamide triazole; CaRest M3; CARN 700; cartilage-derived inhibitors; casein kinase inhibitors (ICOS); castanospermine; cetrorelix; chlorins; chloroquinoxalinesulfonamide; cicaprost; cis-porphyrin; clomiphene analogs; clotrimazole; collismycin A; collismycin B; combretastatin A4; combretastatin analogs; conagenin; crambescidin 816; crisnatol; cryptophycin 8; cryptophycin A derivatives; curacin A; cyclopentanthraquinones; cycloplatam; cypemycin; cytarabine ocfosfate; cytolytic factor; cytostatin; dacillin; daunomycin glucuronide; daunomycin; dehydrodidemnin B B); diethylstilbestrol; deslorelin; dexamethasone;dexifosfamide; dexrazoxane; dexverapamil; didemnin B; didox; diethylnorspermine; azacytidine; dihydro-5-azacytidine; 9-dihydropaclitaxel; dioxamycin; diphenylspiromustine; docosanol; dolasetron; doxifluridine; dronabinol; duocarmycin SA; ebselen; eticomustine; edelfosine; edrecolomab; eflomithine; elemene; ethiprofen; epirubicin; aprepitant; estrogen mustard analogs; estrogen agonists; estrogen antagonists; etanidazole; ethinyl estradiol; etoposide phosphate; exemestane; filgrastim; finasteride; flavopiridol; fluasterone; fludarabine Labine; fludaunorubicin hydrochloride; fomemax; formestane; fotemustine; gadolinium texasporphyrin; gallium nitrate; galocitabine; ganirelix; gelatinase inhibitors; glutathione inhibitors; hepsulfam; heregulin; hexamethylenebisacetamide; hypericin; ibandronic acid; idoxifene; idromone; imofosine; ilomastat; imidazoacridone; imiquimod; immunostimulatory peptides; insulin-like growth factor-I receptor inhibitors; interferon agonists; interferons; interleukins; iodobenzylguanidine; iodoxorubicin; 4-dipotarol; irinotecan; iroplak; irsogladine; isobengazole; isohomohalicondrin B; itasetron; jasplakinolide; kahalalide F; lamellarin-N triacetate; lanreotide; leinamycin; lenograstim; lentinan sulfate; leptolstatin; leukemia inhibitory factor; interferon-alpha; leuprolide + estrogen + progesterone; leuprolide; levamisole; lirazole; linear polyamine analogs; lipophilic disaccharide peptides; lipophilic platinum compounds; lissoclinamide 7; lobaplatin; earthworm phospholipids; lometrexol; lonidamine; losoxantrone; lovastatin; loxoribine; lutetium texas porphyrin; lysofylline; lytic peptides; maytansine; mannostatin A; marimastat; masorofol; maspin; matrix lytic factor inhibitors; matrix metalloproteinase inhibitors; merbarone; meterelin; methioninase; metoclopramide; MIF inhibitors; mifepristone; miltefosine; milistostim; mismatched double-stranded RNA; mitoguanidine; dibromodulanol; mitomycin analogs; mitonadamide; mitotoxin fibroblast growth factor-saporin; mofaroten; molasses; monoclonal antibodies, human chorionic gonadotropin; monophosphoryl lipid A+ mycobacterial cell wall sk; mopidamol; multidrug resistance gene inhibitors; multiple tumor suppressor 1-based therapies;Mustard anticancer compound; mycaperoxide B; mycobacterial cell wall extract; myriaporone; N-acetyldinaline; N-substituted benzamides; nafarelin; nagrestip; naloxone + pentazocine; napavin; naphterpin; narostim; nedaplatin; nemorubicin; neridronic acid; neutral endopeptidase; nilutamide; nisamycin; nitric oxide modulator; nitric oxide antioxidant; nitrullyn; O6-benzylguanine; octreotide; okicenone; oligonucleotide; onapristone; ondansetron; ondansetron; oracin; oral cytokine inducer; oxaliplatin; oxaunomycin; paclitaxel analog; paclitaxel derivative; palauamine; palmitoylrhizoxin; pamidronate; panaxatriol; panomifen; parabactin; palazeptine ; Pegaspargase; Pedicin; Pentosan polysulfate sodium; Pentostatin; Pentrozole; Perflurane; Perphosphamide; Perillyl alcohol; Phenazine; Phenylacetate; Phosphatase inhibitors; Hemolytic Streptococcal preparations; Pilocarpine hydrochloride; Pirarubicin; Pirtrexine; Placenta A; Placenta B; Plasminogen activator inhibitors; Platinum complexes; Platinum compounds; Platinum triamine complexes; Porfimer sodium; Porfiromycin; Propyl diacridone; Prostaglandin J2; Proteasome inhibitors; protein A-type immunomodulators; protein kinase C inhibitors; protein kinase C inhibitors, microalgal; protein tyrosine phosphatase inhibitors; purine nucleoside phosphorylase inhibitors; purpurins; pyrazoloacridines; pyridoxal hemoglobin polyoxyethylene conjugates; Raf antagonists; raltitrexed; ramosetron; Ras farnesyl protein transferase inhibitors; Ras inhibitors; Ras-GAP inhibitors; demethylated reteptine; rhenium (Re) 186-hydroxyethidronate; rhizoxin; ribozyme; RII retinamide; rohitukine; romotide; roquineme; rubiginone B1; ruboxyl; saintopin; SarCNU; sarcophytol A; sargramostim; Sdi 1 analog; senescence-derived inhibitor 1; sense oligonucleotide; signal transduction inhibitor; signal transduction regulator; single-chain antigen-binding protein; sizofuran; SN-38; sobuzoxane; borcarbazone sodium; sodium phenylacetate; solverol; somatomedin binding protein; sonaramine; fospartate; spicamycin D; spiromustine; splenopentin; spongistatin 1; squalamine; stem cell inhibitor; stem cell division inhibitor; stipiamide; stromelysin inhibitor; sulfinosine;Superactive vasoactive intestinal peptide antagonist; suradista; suramin; swainsonine; synthetic aminodextran; tamustine; tamoxifen; tamoxifen methyliodide; tauromustine; taxanes; tazarotene; tecogalan sodium; tegafur; tellurapyrylium; telomerase inhibitors; temozolomide; testosterone propionate, tetrachlorodecoxide; tetrazolamine; phageblastin; thalidomide; thiazolidine; thrombopoietin; thrombopoietin mimetics; thrombopoietin adenofasine; thymopoietin receptor agonist; thymotreonam; thyrotropin; ethyltin purpurogen; titanium dichloride; topsentin; toremifene; totipotent stem cell factor; translation inhibitor; tretinoin; triacetyluridine; triciribine; tropisetron; turotelene; tyrosine kinase inhibitor; tyrosine phosphorylation inhibitor; UBC inhibitor; ubenimex; urogenital sinus-derived growth inhibitory factor; urokinase receptor antagonist; variolin B; vector system, erythrocyte gene therapy; verarezolin; veramine; verdins; vinorelbine; vinxaltine; vitamin; zanoterone; zilascorb; zinostatin stimalamer; abrin; ricin; ribonuclease; onconase; rapLR1; DNase I; Staphylococcal enterotoxin-A; pokeweed antiviral protein; gelonin; diphtheria toxin; Pseudomonas exotoxin; Pseudomonas endotoxin; or a combination of these. ;

[1436] In some embodiments, the drug used in combination with the disclosed compounds is selected from the group consisting of: duocarmycin and its analogs, dolatin, combretastatin, calicheamicin, N-acetyl-γ-calicheamicin (CMC), calicheamicin derivatives, maytansine and its analogs, DM-I, auristatin E, auristatin EB (AEB), auristatin EFP (AEFP), monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), tubulysin, bisoprazole, epothilones, paclitaxel, docetaxel, tocopherol, dapoxetine ... Protecan, echinomycin, estramustine, cemadotin, eleutherobin, methopterin, actinomycin, daunorubicin, daunorubicin conjugate, mitomycin C, mitomycin A, vincristine, retinoic acid, camptothecin, camptothecin derivatives, SN38, maytansine, maytansine alkaloid-type derivatives, DM1, DM4, TK1, amanitin, pyrrolobenzodiazepine, pyrrolobenzodiazepine dimer, methotrexate, elomedin, aspirin, IMID, lenalidomide, pomalidomide.

[1437] The compounds of the present application may also be used in combination with any of the following treatments:

[1438] Combination therapy with compounds targeting the androgen receptor, including androgen depletion methods and antiandrogens. Such inhibitors include, but are not limited to, enzalutamide, apalutamide, darolutamide, and the like.

[1439] Treatment in combination with poly (ADP-ribose) polymerase (PARP) inhibitors, which are a class of chemotherapeutic agents targeting cancers with defective DNA-damage repair (Yuan et al., Expert Opin Ther Pat, 2017, 27:363). Such PARP inhibitors include, but are not limited to, olaparib, rucapabor, velapabor, nirapabor, talazopabor, pamipabor, inipabor, E7449, and A-966492.

[1440] With the signal transduction pathway and mechanism of repair that causes DNA single-strand and double-strand breaks, for example, the treatment of the inhibitor combination of nuclear factor-κB signal transduction (Pilie et al., Nat Rev Clin Oncol, 2019, 16: 81;Zhang et al., Chin J Cancer, 2012, 31: 359).Such inhibitors include but are not limited to inhibitors of ATM and ATR kinases, checkpoint kinases 1 and 2, DNA-dependent protein kinases and WEE1 kinases (Pilie et al., Nat Rev Clin Oncol, 2019, 16: 81).

[1441] The present invention relates to immunomodulators (Khalil et al., Nat Rev Clin Oncol, 2016, 13:394), cancer vaccines (Hollingsworth et al., NPJ Vaccines, 2019, 4:7), immune checkpoint inhibitors (e.g., PD-1, PD-L1, CTLA-4 inhibitors) (Wei et al., Cancer Discov, 2018, 8:1069), cyclin D-kinase 4 / 6 inhibitors (Goel et al., Trends Cell Biol, 2018, 28:911), antibodies capable of binding to tumor cells and / or metastases and inducing antibody-dependent cellular cytotoxicity (ADCC) (Kellner et al., Transfus Med Hemother, 2017, 44:327), T cell or NK cell engagers (e.g., bispecific antibodies) (Yu et al., J Cancer Res Clin Oncol, 2019, 145:941), cell therapy using expanded autologous or allogeneic immune cells (e.g., chimeric antigen receptor T (CAR-T) cells) (Khalil et al., Nat Rev Clin Oncol, 2016, 13:394) combined therapy. Immune checkpoint inhibitors include but are not limited to nivolumab, ipilimumab, pembrolizumab, atezolizumab, avelumab, durvalumab, and cemiplimab.

[1442] According to the present application, the compound can be administered before, simultaneously with, or after other anti-cancer compounds. The administration regimen may involve administering different active agents in an alternating manner. In other embodiments, the compound can be delivered before and during, or during and after, or before and after, or before, during, and after treatment with other therapies. In some embodiments, the compound is administered more than 24 hours before administering another anti-proliferative therapy. In some embodiments, more than one anti-proliferative therapy may be administered to a subject. For example, a subject may receive a compound of the invention in combination with surgery and at least one other anti-proliferative compound. In some embodiments, the compound may be administered in combination with more than one anti-cancer drug.

[1443] In some embodiments, the compounds of the present application are used to detect cells and tissues that overexpress PSMA, whereby such detection is achieved by conjugating a detectable label to the compounds of the present application (e.g., a detectable radionuclide) or by attaching a dye to a peptide. In some embodiments, the cells and tissues detected are diseased cells and tissues and / or are the cause or etiology of the disease and / or symptoms of the disease, or are part of the underlying pathology of the disease. In some embodiments, the diseased cells and tissues cause and / or are part of an oncology indication (e.g., a tumor, a tumour, and a cancer).

[1444] In some embodiments, the compounds of the present application are used to treat cells and tissues that overexpress prostate-specific membrane antigen (PSMA). In some embodiments, the cells and tissues being treated are diseased cells and tissues and / or are the cause of the disease and / or symptoms of the disease, or are part of the underlying pathology of the disease. In some embodiments, the diseased cells and tissues cause and / or are part of an oncology indication (e.g., a tumor, a tumour, and a cancer), and the therapeutic activity is achieved by conjugating a therapeutically active nuclide to the compounds of the present application (e.g., a therapeutically active radionuclide).

[1445] In another embodiment, the compound of the present application is administered in a therapeutically effective amount. In some embodiments, a therapeutically effective amount is a compound dosage sufficient to provide treatment or medically desired results or effects in the subject to which the compound is administered. A therapeutically effective amount will vary with the specific condition being treated, the age and physical condition of the subject being treated, the severity of the condition, the duration of treatment, the nature of the combined therapy (if any), specific routes of administration, and other factors within the knowledge and expertise of the healthcare practitioner. For example, with respect to methods involving treatment of a subject having a condition characterized by abnormal cell proliferation, the effective amount of suppressing proliferation will be the amount sufficient to reduce or completely stop abnormal cell proliferation, to slow down or stop the development or progress of cell mass (such as tumor). In one embodiment, and as preferably used herein, the term "suppression" includes all of the foregoing.

[1446] In some embodiments, a therapeutically effective amount will be that amount required to prolong the dormancy of micrometastases or stabilize any residual primary tumor cells following surgical or medical treatment.

[1447] Typically, the therapeutically effective amount can vary based on factors such as the age, condition and sex of the subject and the nature and degree of the subject's disease, all of which can be determined by those of ordinary skill in the art. Dosage can be adjusted by an individual doctor or veterinarian, particularly in the case of any complication. In some embodiments, the therapeutically effective amount includes but is not limited to the amount within the scope of 0.1 μg / kg to about 2000 mg / kg, or 1.0 μg / kg to about 1000 mg / kg, or about 0.1 mg / kg to about 500 mg / kg, or about 1.0 mg / kg to about 100 mg / kg, for example, administered once or multiple times a day. If desired, the effective daily dose of the active compound can be administered as two, three, four, five, six or more sub-doses, for example, administered separately at appropriate intervals all day, optionally administered in unit dosage form. In some embodiments, the compound is administered for more than 7 days, more than 10 days, more than 14 days or more than 20 days. In some embodiments, the compound is administered within the time period of several weeks or months or years. In some embodiments, the compound is delivered at alternating days. For example, the pharmaceutically active agent is delivered every two days, or every three days, or every four days, or every five days, or every six days, or every week, or every month.

[1448] In some embodiments, the compounds of the present application are used to treat and / or prevent a disease, wherein such treatment is radionuclide therapy.

[1449] For example, radionuclide therapy utilizes or is based on different forms of radiation emitted by radionuclides. For example, such radiation can be photon radiation, including but not limited to beta - Any of electron radiation of particles and Auger electrons, proton radiation, neutron radiation, positron radiation, alpha particle radiation or ion beam. Depending on the type of particles or radiation emitted by the radionuclide, radionuclide therapy can, for example, be distinguished as photon radionuclide therapy, electron radionuclide therapy, proton radionuclide therapy, neutron radionuclide therapy, positron radionuclide therapy, alpha particle radionuclide therapy or ion beam radionuclide therapy. The present application encompasses all of these forms of radionuclide therapy, and all of these forms of radionuclide therapy can be achieved by the compounds of the present application, wherein the radionuclide attached to the compounds of the present application provides such radiation.

[1450] Radionuclide therapy works by damaging the DNA of cells. The damage is caused by direct or indirect ionization of the atoms that make up the DNA chain by photons, electrons, protons, neutrons, positrons, alpha particles, or ion beams. Indirect ionization occurs due to the ionization of water, forming free radicals, particularly hydroxyl radicals, which then damage DNA.

[1451] In the most common forms of radionuclide therapy, the majority of radiation's effects are through free radicals. Because cells possess mechanisms to repair DNA damage, damaging both strands of DNA has proven to be a promising technique for modifying cellular characteristics. Because cancer cells are often undifferentiated and stem-like, they replicate more rapidly than most healthy, differentiated cells and have a reduced ability to repair sublethal damage. DNA damage is inherited through cell division, accumulating damage in cancer cells and causing them to die or reproduce more slowly.

[1452] Oxygen is a potent radiosensitizer that increases the effectiveness of a given dose of radiation by forming DNA-damaging free radicals. Thus, high-pressure oxygen tanks, blood substitutes that carry increased oxygen, hypoxic cell radiosensitizers (e.g., misonidazole and metronidazole), and hypoxic cytotoxins (e.g., tirapazamine) can be used.

[1453] Other factors considered in choosing a dose of radiation include whether the patient is receiving chemotherapy, whether the radiation therapy is administered before or after surgery, and how successful the surgery was.

[1454] For one or more of several important reasons, the total radioactive dose may be fractionated, i.e., spread out over time over one or more treatments. For example, fractionation allows normal cells time to recover, whereas tumor cells typically repair less efficiently between treatments. For example, fractionation also allows tumor cells that are in a relatively radioresistant phase of the cell cycle during one treatment to cycle to a more sensitive phase of the cycle before being given the next fraction. Similarly, tumor cells that are chronically or acutely hypoxic and therefore more radioresistant can be reoxygenated between fractions, thereby improving tumor cell killing.

[1455] It's well known that different cancers respond differently to radiation therapy. A cancer's response to radiation is described by its radiosensitivity. Highly radiosensitive cancer cells are rapidly killed by moderate doses of radiation. These include leukemias, most lymphomas, and germ cell tumors.

[1456] It is important to distinguish between the radiosensitivity of a particular tumor (which is, to some extent, a laboratory measurement) and the "curability" of a cancer in actual clinical practice by the dose of radioactivity delivered internally. For example, leukemias are generally not curable with radiotherapy because they are diffuse throughout the body. Lymphomas can be completely curable if they are localized to one area of ​​the body. Similarly, many common, moderately radioresponsive tumors can be treated with a curative dose of radioactivity if they are in the early stages. This applies, for example, to non-melanoma skin cancer, head and neck cancer, non-small cell lung cancer, cervical cancer, anal cancer, and prostate cancer.

[1457] A tumor's response to radiation therapy is also related to its size. For complex reasons, very large tumors do not respond as well to radiation as smaller tumors or microscopic disease. Various strategies are used to overcome this effect. The most common technique is surgical resection before radiation therapy. This is most common in breast cancer treatment with wide local excision or mastectomy followed by adjuvant radiation therapy. Another approach is to shrink the tumor with neoadjuvant chemotherapy before free radical radionuclide therapy. A third technique is to enhance the cancer's radiosensitivity by giving certain drugs during radiation therapy. Examples of radiosensitizing drugs include, but are not limited to, cisplatin, nimozole, and cetuximab.

[1458] Intraoperative radiation therapy is a special type of radiation therapy that is delivered immediately after the cancer is surgically removed. This approach has been used for breast cancer (targeted intraoperative radiation therapy), brain tumors, and colorectal cancer.

[1459] Radionuclide therapy itself is painless. Many low-dose palliative treatments cause minimal or no side effects. Higher-dose treatments can cause different side effects during treatment (acute side effects), months or years after treatment (long-term side effects), or after retreatment (cumulative side effects). The nature, severity, and longevity of these side effects depend on the organ being irradiated, the treatment itself (type of radionuclide, dose, fractionation, concurrent chemotherapy), and the patient.

[1460] Within this application, the methods of the present invention for treating disease may implement each and any of the above strategies known in the art and herein constitute additional embodiments of the present application.

[1461] Within the present application, the compounds of the present application are used in methods for diagnosing diseases as disclosed herein. In some embodiments, such methods include the step of administering a diagnostically effective amount of a compound of the present application to a subject in need thereof.

[1462] According to the present application, the imaging method is selected from the group consisting of scintigraphy, single photon emission computed tomography (SPECT), positron emission tomography (PET), computed tomography, and combinations thereof.

[1463] Scintigraphy is a form of diagnostic test or method used in nuclear medicine in which a radiopharmaceutical is internalized by cells, tissues, and / or organs, for example, in vivo, and the radiation emitted by the internalized radiopharmaceutical is captured by an external detector (gamma camera) to form and display a two-dimensional image. In contrast, SPECT and PET form and display three-dimensional images. Therefore, SPECT and PET are classified as separate techniques from scintigraphy, even though they also use gamma cameras to detect internal radiation. Scintigraphy differs from diagnostic X-rays in that external radiation is passed through the body to form an image.

[1464] Single-photon emission computed tomography (SPECT) scans are a nuclear imaging technique that uses gamma rays. They are very similar to conventional nuclear medicine planar imaging using a gamma camera. Before a SPECT scan, the patient is injected with a radiolabeled chemical that emits gamma rays that can be detected by the scanner. A computer collects the information from the gamma camera and converts it into two-dimensional cross-sections. These cross-sections can be added together to form a three-dimensional image of an organ or tissue. SPECT involves the detection of gamma rays emitted individually and sequentially by the radionuclide provided by the radiolabeled chemical. To acquire SPECT images, the gamma camera rotates around the patient. Projections are acquired at defined points during the rotation (usually every 3-6 degrees). In most cases, a full 360-degree rotation is used to obtain the best reconstruction. The time it takes to acquire each projection is also variable, but 15-20 seconds is typical. This gives a total scan time of 15-20 minutes. Multi-head gamma cameras are faster. Because SPECT acquisition is very similar to planar gamma camera imaging, the same radiopharmaceuticals can be used.

[1465] Positron emission tomography (PET) is a non-invasive diagnostic imaging technique used to measure the biochemical state or metabolic activity of cells in the human body. PET is unique because it produces images of the body's basic biochemistry or function. Traditional diagnostic techniques such as X-rays, computed tomography scans, or MRI produce images of the body's anatomy or structures. These techniques are premised on being able to visualize any structural or anatomical changes associated with disease. Biochemical processes are also altered by disease and can occur before any significant changes in anatomy. PET is an imaging technique that can visualize some of these early biochemical changes. PET scanners rely on radiation emitted from the patient to create images. Each patient is given a tiny dose of a radiopharmaceutical that either closely resembles a natural substance used by the body or binds specifically to a receptor or molecular structure. When the radioisotope undergoes positron emission decay (also known as positive-beta decay), it emits a positron—the antiparticle counterpart of the electron. After traveling up to a few millimeters, the positron encounters an electron and annihilates, producing a pair of annihilation (gamma) photons traveling in opposite directions. These are detected when they reach the scintillating material in the scanning device, generating a burst of light that is detected by a photomultiplier tube or silicon avalanche photodiode. The technology relies on the simultaneous, or coincidental, detection of pairs of photons. Photons that do not arrive in pairs (i.e., within a few nanoseconds) are ignored. All coincidences are forwarded to the image processing unit, where an image reconstruction process is used to generate the final image data.

[1466] SPECT / CT and PET / CT are combinations of SPECT and PET with CT. The key benefit of combining these modalities is increased reader confidence and accuracy. With traditional PET and SPECT, the limited number of photons emitted from an abnormal area creates a very low level of background, making it difficult to locate the area anatomically. Adding CT helps determine the location of the abnormal area anatomically and categorize the likelihood that it represents disease.

[1467] Within this application, the methods of the present invention for treating disease may implement each and any of the above strategies known in the art and herein constitute additional embodiments of the present application.

[1468] In some embodiments, the compounds of the present application can be used to stratify patients, i.e., to create subsets within a patient population that provide more detailed information about how the patient will respond to a given drug. Stratification can be a key component in converting clinical trials from negative or neutral results to clinical trials with positive results by identifying subsets of the population most likely to respond to a new therapy.

[1469] Stratification involves identifying a group of patients with shared “biological” characteristics to select the best management for the patient and achieve the best possible outcome in terms of risk assessment, risk prevention, and achieving the best treatment outcome.

[1470] In some embodiments, the compounds of the present application can be used to assess or detect a particular disease as early as possible (which is a diagnostic use), the risk of developing a disease (which is a susceptibility / risk use), the evolution of the disease (including slow growth and aggressiveness) (which is a prognostic use), and they can be used to predict the response and toxicity to a given treatment (which is a predictive use).

[1471] It is also within the scope of the present application that the compounds of the present application can be used in theranostics. The concept of theranostics is to combine a therapeutic agent with a corresponding diagnostic test that can increase the clinical usefulness of the therapeutic drug. The concept of theranostics is becoming increasingly attractive and is widely recognized as the key to improving the efficiency of drug therapy by helping doctors identify patients who are likely to benefit from a given therapy and thus avoid unnecessary treatment.

[1472] The concept of theranostics is to combine a therapeutic agent with a diagnostic test that allows physicians to identify those patients who will benefit most from a given therapy. In one embodiment, the compounds of the present application are used to diagnose patients, i.e., to identify and localize the primary tumor mass and potential local and distant metastases. In addition, tumor volume can be determined, particularly using three-dimensional diagnostic modalities such as SPECT or PET. Only those patients with PSMA-positive tumor masses and therefore likely to benefit from a given therapy are selected for a specific therapy, thereby avoiding unnecessary treatment. For example, such a therapy is PSMA-targeted therapy using the compounds of the present application. In some embodiments, chemically identical tumor-targeted diagnostics are used, including imaging diagnostics such as scintigraphy, PET, or SPECT, as well as radiotherapy. Such compounds differ only in the radionuclide and therefore generally have very similar (if not identical) pharmacokinetic profiles. This can be achieved using chelators and diagnostic or therapeutic radiometals. Alternatively, this can be achieved using radiolabeled precursors and radiolabeling with diagnostic or therapeutic radionuclides. In one embodiment, diagnostic imaging is used with the aid of quantification of radiation from diagnostic radionuclides known to those skilled in the art and subsequent dose determination and prediction of drug concentrations in tumors compared to vulnerable side effect organs. Thus, truly personalized drug administration therapy for the patient is achieved.

[1473] In some embodiments, theranostic methods are implemented using only one theranostically active compound, such as a compound of the present application labeled with a radionuclide that emits diagnostically detectable radiation (e.g., positrons or gamma rays) as well as therapeutically effective radiation (e.g., electrons or alpha particles).

[1474] The present application also contemplates a method for intraoperatively identifying / disclosing diseased tissue expressing PSMA in a subject. Such methods utilize the compounds of the present application, wherein in some embodiments, such compounds of the present application comprise a diagnostically active agent, such as a diagnostically active radionuclide.

[1475] According to another embodiment of the present application, the compounds of the present application, particularly if complexed with a radionuclide, can be used as an adjuvant or adjuvant to any other tumor treatment, including surgery, which is the primary method of treating most isolated solid cancers, radiation therapy involving the use of ionizing radiation to attempt to cure or ameliorate the symptoms of cancer using sealed internal or external sources in the form of brachytherapy, chemotherapy such as alkylating agents, antimetabolites, anthracyclines, plant alkaloids, topoisomerase inhibitors and other anti-tumor agents, hormonal therapies that modulate tumor cell behavior without directly attacking those cells, targeted agents that directly target molecular abnormalities in certain types of cancer (including monoclonal antibodies and tyrosine kinase inhibitors), angiogenesis inhibitors, immunotherapy, cancer vaccination, palliative care (including the effect of reducing physical, emotional, mental and psycho-social suffering to improve the patient's quality of life) and alternative therapies (including a diverse group of health care systems, practices and products that are not part of conventional medicine).

[1476] In one embodiment of the method of the present application, the subject is a patient. In one embodiment, the patient is a subject who has been diagnosed with a disease or is suspected of having a disease or is at risk of having a disease or developing a disease, wherein the disease is a disease as described herein, a disease involving prostate-specific membrane antigen (PSMA).

[1477] The dosage employed in the practice of the methods for treatment and diagnosis, respectively, wherein a radionuclide is used and more specifically is attached to or is a portion of a compound of the present application, will vary according to, for example, the specific condition to be treated, such as the known radiosensitivity of the tumor type, the volume of the tumor, and the desired therapy. Typically, the dosage is calculated based on the distribution of radioactivity per organ and the observed target uptake. The gamma-emitting complex can be administered once or multiple times for diagnostic imaging. In animals, a specified dose range can be, for example, 0.1 ng / kg to 5 mg / kg of the compound of the present application, in combination with, for example, 1 kBq to 200 MBq of a gamma-emitting radionuclide, including but not limited to 111 In or 89 The alpha-emitting or beta-emitting complexes of the compounds of the present invention can be administered at several time points, for example, over a period of 1 to 3 weeks or longer. In animals, a specified dose range can be, for example, 0.1 ng / kg to 5 mg / kg with, for example, 1 kBq to 200 MBq of an alpha-emitting or beta-emitting radionuclide (including but not limited to 225 Ac or 177 In larger mammals (including, for example, humans), indicated dosage ranges may be, for example, 0.1 ng / kg to 5 mg / kg or, for example, 0.1 ng / kg to 100 μg / kg with, for example, 10 to 1000 MBq of a gamma-emitting radionuclide (including, but not limited to,111 In or 89 In larger mammals (including, for example, humans), indicated dosage ranges may be, for example, 0.1 ng / kg to 5 mg / kg or, for example, 0.1 ng / kg to 100 μg / kg with, for example, 1 to 100,000 MBq of an α- or β-emitting radionuclide (including, but not limited to, 225 Ac or 177 The compound of the present application complexed with Lu).

[1478] In certain embodiments, uptake can be measured in terms of absorbed dose (mGy / MBq), SUVmax and / or SUVmean. In animals, uptake across tissues is reported as percent injected dose / gram (%ID / g). Sensitivity to radiation is tumor and non-tumor tissue dependent. The favorable tumor to non-tumor tissue uptake of the compounds of the present invention allows for the delivery of radionuclides at doses that can reduce tumor growth or partially or completely destroy tumors. At such doses, no permanent or critical damage to non-tumor tissues is expected.

[1479] In another aspect, the present application relates to compositions and pharmaceutical compositions, in particular, comprising the compounds of the present application.

[1480] The pharmaceutical composition of the application comprises at least one compound of the application and optional one or more carrier materials, excipients and / or adjuvants. The pharmaceutical composition can additionally comprise one or more of, for example, water, a buffer (e.g., neutral buffered saline or phosphate buffered saline), ethanol, mineral oil, vegetable oil, dimethyl sulfoxide, a carbohydrate (e.g., glucose, mannose, sucrose or dextran), mannitol, a protein, an adjuvant, a polypeptide or an amino acid (e.g., glycine), an antioxidant, a chelating agent (e.g., EDTA or glutathione) and / or a preservative. In addition, one or more other active ingredients can but need not be included in the pharmaceutical composition of the application.

[1481] The pharmaceutical composition of the present application can be formulated for any appropriate route of administration, including, for example, topical administration, such as transdermal or ocular, oral, buccal, nasal, vaginal, rectal or parenteral administration. In one embodiment, and as preferably used herein, the term parenteral includes subcutaneous, intradermal, intravascular, such as intravenous, intramuscular, intrathecal and intraperitoneal injection, and any similar injection or infusion techniques. In some embodiments, the route of administration is intravenous administration.

[1482] In one embodiment of the present application, the compound of the present application containing a radionuclide is administered by any conventional route, particularly intravenously, for example in the form of an injectable solution or suspension. The compound of the present application can also advantageously be administered by infusion, for example, by infusion over 30 to 60 minutes.

[1483] In some embodiments, depending on the location of the tumor, the compounds of the present application can be administered as close to the tumor site as possible, for example, via a catheter. Such administration can be directly into the tumor tissue or into surrounding tissue or into afferent blood vessels. The compounds of the present application can also be administered in repeated doses, including, in some embodiments, in divided doses.

[1484] According to an embodiment of the present application, the pharmaceutical composition of the present application comprises a stabilizer, such as a free radical scavenger, which inhibits the autoradiolysis of the compound of the present application. Suitable stabilizers include, for example, serum albumin, ascorbic acid, retinol, gentisic acid or a derivative thereof, or an amino acid infusion solution, such as a solution for parenteral protein feeding, such as a solution without electrolytes and glucose, such as a commercially available amino acid infusion solution, such as KE Nephro. In some embodiments, ascorbic acid and gentisic acid are used.

[1485] The pharmaceutical composition of the present application may comprise additional additives, such as reagents for adjusting the pH between 7.2 and 7.4, such as sodium acetate or ammonium acetate or Na2HP04. In some embodiments, a stabilizer is added to the non-radioactive compound of the present application, and in the presence of the stabilizer, the introduction of the radionuclide, such as complexation with the radionuclide, is carried out at room temperature or, for example, at a temperature of 40 to 120°C. The complexation can be conveniently carried out under airless conditions, such as under N2 or Ar. In some embodiments, additional stabilizers may be added to the composition after the complexation.

[1486] Excretion of the compounds of the present application, particularly if the compounds contain radionuclides, occurs primarily through the kidneys. In some embodiments, the excretion of the compounds of the present application can be controlled by administering lysine or arginine or an amino acid solution having a high content of lysine and / or arginine (e.g., commercially available amino acid solutions such as Synthamin) prior to or together with the injection of the compounds of the present application. -14 or -10) to achieve further protection of the kidney from radioactive accumulation, particularly if the compound includes a radionuclide. In some embodiments, instead of amino acid infusion or in addition to amino acid infusion, the protection of the kidney can also be achieved by administering a plasma expander, such as gelofusine. In some embodiments, the protection of the kidney can also be achieved by administering a diuretic, which provides a forced diuretic means for improving urination rate. Such diuretics include high-efficiency loop diuretics, thiazide drugs, carbonic anhydrase inhibitors, potassium-retaining diuretics, calcium-retaining diuretics, osmotic diuretics, and low-efficiency loop diuretics. In some embodiments, in addition to the compound of the present application, the pharmaceutical composition of the present application can contain at least one of these other compounds intended for or suitable for kidney protection (including, for example, kidney protection for a subject administering the compound of the present application).

[1487] Those skilled in the art will appreciate that the compounds disclosed herein are useful in a variety of methods. Those skilled in the art will further appreciate that the compositions and pharmaceutical compositions of the present application can also be used in the various methods described. Those skilled in the art will also appreciate that the compositions and pharmaceutical compositions disclosed herein are useful in a variety of methods. Those skilled in the art will also appreciate that the compounds of the present application can also be used in the various methods described.

[1488] Those skilled in the art will recognize that, in addition to the compounds of the present invention, the compositions and / or pharmaceutical compositions disclosed herein may contain one or more additional compounds. To the extent that such one or more additional compounds are disclosed herein as part of the compositions and / or pharmaceutical compositions of the present invention, it will be understood that such one or more additional compounds may be administered separately from the compounds of the present invention to the exposed subject or the subject of the method of the present invention. Such administration of one or more other compounds may be performed before, simultaneously with, or after the administration of the compounds of the present invention. Those skilled in the art will also recognize that, in the methods of the present invention, in addition to the compounds of the present invention, one or more additional compounds may be administered to the subject. Such administration of one or more additional compounds may be performed before, simultaneously with, or after the administration of the compounds of the present invention. To the extent that such one or more additional compounds are disclosed herein as being administered as part of the methods of the present invention, it will be understood that such one or more additional compounds are part of the compositions and / or pharmaceutical compositions of the present invention. Within the present application, the compounds of the present invention and the one or more additional compounds may be contained in the same or different formulations. It is also within the present application that the compound of the present application and one or more additional compounds are not contained in the same formulation, but are contained in the same package, said package containing a first formulation comprising the compound of the present application and a second formulation comprising the one or more additional compounds, whereby the types of formulations may be the same or may be different.

[1489] In the present application, the composition and / or pharmaceutical composition of the present application may contain more than one type of compound of the present application. In the present application, more than one type of compound of the present application may also be used in the method of the present application, preferably administered.

[1490] It will be appreciated that the compositions of the present application and the pharmaceutical compositions of the present application may be manufactured in conventional manner.

[1491] Radiopharmaceuticals have a radioactivity content that decreases over time due to radioactive decay. The physical half-life of the radionuclide is usually very short for radiopharmaceutical diagnostics. In these cases, final preparation must be performed shortly before administration to the patient. This is particularly true for positron-emitting radiopharmaceuticals (PET radiopharmaceuticals) used for tomography. This often results in the use of semi-finished products, such as radionuclide generators, radioactive precursors, and test kits.

[1492] In some embodiments, in addition to one or more compounds of the present application, the kits of the present application typically contain at least one of the following: instructions for use, final preparation and / or quality control, one or more optional excipients, one or more optional reagents for labeling procedures, optional one or more radionuclides (with or without shielding containers) and optional one or more devices, wherein the devices are selected from labeling devices, purification devices, analytical devices, processing devices, radiation protection devices or administration devices.

[1493] Shielded containers called "pigs" used for general handling and transport of radiopharmaceutical containers have various configurations for holding radiopharmaceutical containers, such as bottles, vials, syringes, etc. One form includes a removable cover that allows access to the held radiopharmaceutical container. When the pig cover is in place, radiation exposure is acceptable.

[1494] In some embodiments, the labeling device is selected from the group consisting of an open reactor, a closed reactor, a microfluidic system, a nanoreactor, a cartridge, a pressure vessel, a vial, a temperature-controlled reactor, a mixing or shaking reactor, and combinations thereof.

[1495] In some embodiments, the purification device is selected from the group consisting of an ion exchange chromatography column or device, a size exclusion chromatography column or device, an affinity chromatography column or device, a gas or liquid chromatography column or device, a solid phase extraction column or device, a filtration device, a centrifugal vial column or device, and combinations thereof.

[1496] In some embodiments, the analytical device is selected from a test or test device to determine the identity, radiochemical purity, radionuclide purity, radioactivity content, and specific activity of a radiolabeled compound, and combinations thereof.

[1497] In some embodiments, the processing device is selected from the group consisting of devices for mixing, diluting, dispensing, labeling, injecting, and administering radiopharmaceuticals to a subject, and combinations thereof.

[1498] In some embodiments, a radiation protection device is used to protect doctors and other personnel from radiation when using therapeutic or diagnostic radionuclides. In some embodiments, the radiation protection device is selected from the group consisting of a device having a protective barrier of radiation absorbing material, a device that ensures sufficient distance from the radiation source, a device that reduces the time of exposure to the radionuclide, a device that limits the inhalation, ingestion or other mode of entry of radioactive materials into the body, and a device that provides a combination of these measures, wherein the radiation absorbing material is selected from the group consisting of aluminum, plastic, wood, lead, iron, lead glass, water, rubber, plastic, and cloth.

[1499] In some embodiments, the administration device is selected from the group consisting of a syringe, a shielded syringe, a needle, a pump, and an infusion set, and combinations thereof. A syringe shield is typically a hollow cylindrical structure that fits over the cylindrical body of a syringe and is made of lead or tungsten with a lead glass window that allows the operator to view the syringe plunger and the volume of liquid in the syringe. Example

[1500] The following examples have been included to provide guidance to those of ordinary skill in the art for implementing the representative embodiments of the subject matter disclosed herein. According to the application and the general skill level of this area, it will be appreciated by those skilled in the art that the following examples are merely exemplary and, without departing from the scope of the currently disclosed subject matter, may be used for many changes, modifications, and variations. The following synthesis description and specific examples are merely intended to be used for illustrative purposes and should not be construed as limiting in any way the compounds prepared herein by alternative methods.

[1501] The abbreviations used in this application, especially in the following examples, are as follows:

[1502]

[1503]

[1504]

[1505]

[1506] Example 1: Materials, Instruments and Methods

[1507] The materials and methods, as well as the general procedures, are further illustrated by the following examples.

[1508] Material:

[1509] Solvent:

[1510] Solvents were used in the specified quantities without further purification: acetonitrile (Super Gradient, HPLC, VWR, for analytical purposes; PrepSolv, Merck, for preparative purposes); dichloromethane (synthetic grade, Roth); dimethyl sulfoxide (for preparative HPLC: BioScience Grade, Roth, for synthesis: pure, Thermo Scientific), ethyl acetate (synthetic grade, Roth); N,N-dimethylformamide (peptide synthesis grade, Biosolve); 1-methyl-2-pyrrolidone (peptide grade, IRISBioTech); 1,4-dioxane (reinst, Roth); methanol (pa, Merck); cyclohexane (synthetic, Roth); methyl tert-butyl ether (synthetic grade, Roth); water (Milli-Q Plus, Millipore, demineralized).

[1511] Chemicals:

[1512] Chemicals were synthesized according to or similar to literature methods or purchased from Sigma-Aldrich-Merck (Deisenhofen, Germany), Bachem (Bubendorf, Switzerland), VWR (Darmstadt, Germany), Novabiochem (Merck Group, Darmstadt, Germany), Acros Organics (distribution company Fisher Scientific GmbH, Schwerte, Germany), Iris Biotech (Marktredwitz, Germany), Amatek Chemical (Jiangsu, China), Roth (Karlsruhe, Germany), Molecular Devices (Chicago, IL, USA), Biochrom (Berlin, Germany), Peptech (Cambridge, MA, USA), Synthetech (Albany, OR, USA), Pharmacore (High Point, NC, USA), PCAS Biomatrix Inc (Saint-Jean-sur-Richelieu, Quebec, Canada), Alfa Compounds were obtained from Aesar (Karlsruhe, Germany), Tianjin Nankai Hecheng S&T Co., Ltd (Tianjin, China), CheMatech (Dijon, France), JenKem Technology (Plano, TX, USA), Trimen Chemicals (Lodz, Poland), and Anaspec (San Jose, CA, USA) or other companies and used at the indicated quality grade without further purification.

[1513] Solid phase synthetic resins and resin joints:

[1514] Solid-phase synthesis was performed on polystyrene resin (PS: polystyrene cross-linked with 1,4-divinylbenzene or DEG: polystyrene cross-linked with diethylene glycol-dimethacrylate) or ChemMatrix resin (CM) modified with Rink amide, 2-chloro-trityl, 4-methyltrityl, or FMPB (4-formyl-3-methoxy-phenoxybutyl) linkers. For the synthesis of peptide alcohols, preloaded 2-chloro-trityl resin (PS) was used.

[1515] Apparatus and Instruments-Methods:

[1516] HPLC / MS analysis:

[1517] HPLC / MS analysis was performed by injecting 5 μl of sample solution. All chromatograms used a 2-step gradient (5-65% B in 12 minutes, followed by 65-90% B in 0.5 minutes, A: 0.1% TFA in water and B: 0.1% TFA in ACN). RP columns were purchased from Dr. Maisch (ReproSil-Pur 120C18-AQ, 3 μm, 50×3.00 mm, flow rate 0.8 mL, HPLC, room temperature); mass spectrometer: Agilent 6230 LC / TOF-MS or Agilent 6530 LC / Q-TOF-MS, ESI ionization. MassHunter Qualitative Analysis B.07.00.SP2 was used as the software. UV detection was performed at λ = 230 nm. Retention time (R t ) is indicated in the decimal system (e.g., 1.9 min = 1 min 54 s) and refers to detection in a UV spectrometer. To evaluate the observed compound masses, the "Find Compounds by Formula" feature was used. More specifically, individual "Compound Neutral Mass (Daltons)" values ​​and the corresponding isotopic distribution pattern were used to confirm compound identity. The mass spectrometer has an accuracy of approximately ±5 ppm.

[1518] Product purification method - preparative HPLC:

[1519] On a reverse phase column (generally used: Kinetex 5μXB-C18) as the stationary phase Preparative HPLC separations were performed on a 150 x 30 mm column (Phenomenex). 0.1% TFA in water (A) and 0.1% TFA in acetonitrile (B) were used as mobile phases, mixed in a linear binary gradient. The gradient was described as: "10% to 40% B in 30 minutes", which means that a linear gradient from 10% B (and correspondingly 90% A) to 40% B (and correspondingly 60% A) was run in 30 minutes. The flow rate was in the range of 30 to 50 mL / min. A typical gradient used to purify the compounds of the invention starts from 5-25% B and ends at 35-50% B after 30 minutes. The difference between the percentage of B at the end and the beginning is at least 10%. A commonly used gradient is "15% to 40% B in 30 minutes". The sample is preferably dissolved in a mixture of HOAc and water or DMSO.

[1520] Product purification method - solid phase extraction (SPE):

[1521] In the case of solid phase extraction, 250mg Varian Bondesil-ENV is placed in a 15mL polystyrene syringe. Pre-wash the post with methanol (1 × 5mL) and water (2 × 5mL), then the reaction solution or the solution containing product to be purified is applied to the post. In order to remove excessive salt, the post is washed with water (2x5mL) again. Then, the product is eluted with the aqueous solution (first fraction) of 50%ACN of 5mL, subsequently with the aqueous solution containing 0.1%TFA of 50%ACN of at least 5mL, or until the elution of compound is complete.

[1522] Automated / semi-automatic solid phase synthesis equipment:

[1523] Automated solid phase synthesis of peptides and polyamides was performed on a Tetras peptide synthesizer (Advanced ChemTech) at a scale of 25 μmol, 50 μmol, or 100 μmol. Manual steps were performed in plastic syringes equipped with a glass frit (material PE, Roland Vetter Laborbedarf OHG, Ammerbuch, Germany). Coupling at elevated temperature was performed on a Chorus peptide synthesizer (Gy...

Claims

1. A compound of formula (I) or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, in X is selected from a bond and -CH2-; Z 1 Selected from chelating agents and NT; NT is selected from the group consisting of H, Ac, Hex, HPA, HO-succinyl, SaPr, Iva, HYDAc, Bio, nBuCAyl, AF488Ahx, and Hib; L 1 Selected from bonds and -(Xaa1) k -, k is selected from 1, 2 and 3, Xaa1 is each independently an amino acid residue, preferably, the amino acid residue is selected from α-amino acid residue, β-amino acid residue, γ-amino acid residue, δ-amino acid residue, ε-amino acid residue, ω-amino acid residue and an amino acid residue of formula (YI), g is an integer selected from 0 to 23, in, If k = 1, then Xaa1 and Z 1 covalently bound to and covalently bound to Xaa2, If k=2, then the first of the two Xaa1 and Z 1 covalently bound to and covalently bound to the second of the two Xaa1s, and the second of the two Xaa1s is covalently bound to the first of the two Xaa1s and covalently bound to Xaa2, If k=3, then the first of the three Xaa1 and Z 1 covalently bound to and covalently bound to a second of the three Xaa1s, the second of the three Xaa1s is covalently bound to a first of the three Xaa1s and covalently bound to a third of the three Xaa1s, and the third of the three Xaa1s is covalently bound to a second of the three Xaa1s and covalently bound to Xaa2; Among them, when L 1 When Z is a key, 1 is NT; Xaa2 is selected from formula (II) and formula (III): Where R 2a Selected from H, (C1-C6) alkyl and CH2R 2g ; R 2g Selected from OH and CO2H; R 2b is selected from H and (C1-C6)alkyl; Or, R 2a and R 2b can form a 5- or 6-membered carbocyclic or heterocyclic ring together, R 2c is selected from H and CH3; R 2d is selected from H, F and OH; R 2e Selected from H and F; R 2f is selected from H and CH3; The condition is that when L 1 Xaa2 may not be present when it is a bond and NT is Hib; Xaa3 is selected from formula (IV): Where R 3a is selected from the group consisting of aryl, (C5-C6)heteroaryl, indol-3-yl, 6-chloro-1H-indol-3-yl and -S-CH2-phenyl; and wherein R 3a The aryl or heteroaryl ring is optionally substituted with 1, 2 or 3 substituents independently selected from halogen, (C1-C6)alkyl, CN, OH, -O(C1-C3)alkyl, wherein the (C1-C6)alkyl may be optionally substituted with one or more fluorine; R 3b is selected from H and CH3; h is selected from 1 and 2; Xaa5 is selected from the group consisting of Formula (Va), Formula (Vb), Hgn, Lys, Nle, Tap, Aph and Gln: Where R 5a Selected from H, (C1-C6) alkyl, Ac, C(=NR 5d )NR 5e R 5f and Bio; R 5d is selected from H and CH3; R 5e and R 5f Independently selected from H and (C1-C6)alkyl; R 5b is selected from H and (C1-C6)alkyl; R 5c Selected from H and CH3; m is selected from 2, 3, 4 and 5; and R 5g , R 5h and R 5i Independently selected from (C1-C6)alkyl; Xaa6 is selected from Formula (VI), Formula (VII), Nle and arg: Where R 6a Selected from H, C(=NR 6e )NR 6f R 6g 、C(=O)R 6h and pyridyl; R 6e is selected from H and CH3; R 6f Selected from H, (C1-C6) alkyl, Ac, NO2 and C(=O)NR 6i R 6j ; R 6i and R 6j independently selected from H and (C1-C2)alkyl; R 6g is selected from H and (C1-C6)alkyl; Or, R 6e and R 6f They can form a 5- or 6-membered heterocyclic ring. R 6h Selected from (C1-C6) alkyl, NR 6k R 6m and NR 6n C(=NR 6p )NR 6q R 6r ; R 6k and R 6m Independently selected from H and (C1-C6)alkyl; R 6n and R 6p Independently selected from H and CH3; R 6q and R 6r Independently selected from H and (C1-C6)alkyl; R 6b is selected from H and (C1-C6)alkyl; R 6c is selected from H and CH3; n is selected from 1, 2, 3 and 4; R 6d Selected from NR 6s C(=NR 6t )NR 6u R 6v , OH and NR 6w R 6x ; R 6s and R 6t Independently selected from H and CH3; R 6u , R 6v , R 6w and R 6x is independently selected from H and (C1-C6)alkyl; and q is selected from 2, 3 and 4; Xaa7 is an amino acid residue, wherein the amino acid residue is preferably selected from Formula (VIII), Formula (IX), Formula (X), Formula (XI), Dtc and Oic: Where R 7a Selected from H, (C1-C6) alkyl and (CH2) t R 7g ; R 7g Selected from OH, CO2H and NR 7h R 7i ; R 7h and R 7i Independently selected from H and (C1-C6)alkyl; t is selected from 1, 2, 3 and 4; R 7b is selected from H and (C1-C6)alkyl; Or, R 7a and R 7b can form a 5- or 6-membered carbocyclic or heterocyclic ring together, R 7c is selected from H and CH3; R 7d is selected from H, F and OH; R 7e Selected from H and F; R 7f is selected from H and CH3; u is selected from 2, 3 and 4; L 3 Selected from bonds and -(Xab1) v -; Where v is selected from 1, 2 and 3, Xab1 is each independently an amino acid residue, preferably, the amino acid residue is selected from α-amino acid residue, β-amino acid residue, γ-amino acid residue, δ-amino acid residue, ε-amino acid residue, ω-amino acid residue and an amino acid residue of formula (YI), If v = 1, then Xab1 and Z 3 covalently bonded to the side chain amino functional group of formula (X) or formula (XI), If v=2, then the first of the two Xab1 and Z 3 covalently bound to the second of the two Xab1, and the second of the two Xab1 is covalently bound to the first of the two Xab1 and covalently bound to the side chain amino functional group of formula (X) or formula (XI), If v=3, then the first of the three Xab1 and Z 3 covalently bound to the second of the three Xab1s and covalently bound to the third of the three Xab1s, and the third of the three Xab1s is covalently bound to the second of the three Xab1s and covalently bound to the side chain amino functional group of formula (X) or formula (XI); Z 3 Selected from H and a chelating agent; Xaa8 is an α-amino acid residue, wherein the α-nitrogen atom of Xaa8 is unsubstituted or optionally substituted with CH3; Xaa10 is formula (XII): in: R 10a Selected from (C1-C6) alkyl; R 10b is selected from H and (C1-C6)alkyl; Or, R 10a and R 10b can form a 5- or 6-membered carbocyclic or heterocyclic ring together, R 10c is selected from H and CH3; L 2 Selected from: bond and -Xaa11-(Xaa12) s -, so that Xaa11 and Xaa10 are covalently bound; Xaa11 is an amino acid residue, wherein the amino acid residue is preferably selected from the group consisting of an α-amino acid residue, a β-amino acid residue, a γ-amino acid residue, a δ-amino acid residue, an ε-amino acid residue, an ω-amino acid residue and an amino acid residue of formula (YI); s is selected from 0, 1, 2, 3, 4 and 5; and Xaa12 are each independently an amino acid residue, wherein the amino acid residue is preferably selected from the group consisting of an α-amino acid residue, a β-amino acid residue, a γ-amino acid residue, a δ-amino acid residue, an ε-amino acid residue, an ω-amino acid residue and an amino acid residue of formula (YI), If s = 0, then Xaa11 and Z 2 Covalent bonding, If s = 1, Xaa12 is covalently bound to Xaa11 and to Z 2 Covalent bonding, If s=2, the first of the two Xaa12 is covalently bound to Xaa11 and covalently bound to the second of the two Xaa12, and the second of the two Xaa12 is covalently bound to the first of the two Xaa12 and covalently bound to Z. 2 Covalent bonding, If s=3, the first of the three Xaa12 is covalently bound to Xaa11 and covalently bound to the second of the three Xaa12, the second of the three Xaa12 is covalently bound to the first of the three Xaa12 and covalently bound to the third of the three Xaa12, and the third of the three Xaa12 is covalently bound to the second of the three Xaa12 and covalently bound to Z. 2 Covalent bonding, If s=4, the first of the four Xaa12 is covalently bound to Xaa11 and covalently bound to the second of the four Xaa12, the second of the four Xaa12 is covalently bound to the first of the four Xaa12 and covalently bound to the third of the four Xaa12, the third of the four Xaa12 is covalently bound to the second of the four Xaa12 and covalently bound to the fourth of the four Xaa12, and the fourth of the four Xaa12 is covalently bound to the third of the four Xaa12 and covalently bound to Z. 2 Covalent bonding, If s=5, the first of the five Xaa12s is covalently bound to Xaa11 and to the second of the five Xaa12s, the second of the five Xaa12s is covalently bound to the first of the five Xaa12s and to the third of the five Xaa12s, the third of the five Xaa12s is covalently bound to the second of the five Xaa12s and to the fourth of the five Xaa12s, the fourth of the five Xaa12s is covalently bound to the third of the five Xaa12s and to the fifth of the five Xaa12s, and the fifth of the five Xaa12s is covalently bound to the fourth of the five Xaa12s and to Z. 2 covalent binding; Z 2 An α-amino acid residue selected from CT, XDa-chelators and formula (CT-I): CT is selected from the group consisting of formula (CT-II), formula (CT-III), AF488N3K-NH2, OH and Throl-OH: in: R CT1 is selected from H and CH3; R CT2 is selected from H and (C1-C6)alkyl; R CT3 and R CT4 Each independently selected from H and CH3; R CT5 is selected from H and (C1-C6)alkyl; x is selected from 2-10; XDa is a diamine, wherein the diamine is preferably selected from en and Ape; w is selected from 1, 2, 3, 4, 5 and 6; L 4 Select from bonds and -(Xac1) y -, in: y is selected from 0, 1, 2 and 3, Xac1 is each independently an amino acid residue, preferably, the amino acid residue is selected from α-amino acid residue, β-amino acid residue, γ-amino acid residue, δ-amino acid residue, ε-amino acid residue, ω-amino acid residue and an amino acid residue of formula (YI), If y=0, the side chain amino functional group of the α-amino acid residue of formula (CT-I) is 4 Covalent bonding, If y=1, Xac1 is covalently bound to the side chain amino functional group of the α-amino acid residue of formula (CT-I) and to Z 4 Covalent bonding, If y=2, the first of the two Xac1 is covalently bound to the side chain amino functional group of the α-amino acid residue of formula (CT-I) and covalently bound to the second of the two Xac1, and the second of the two Xac1 is covalently bound to the first of the two Xac1 and to Z 4 Covalent bonding, If y=3, the first of the three Xac1s is covalently bound to the side chain amino functional group of the α-amino acid residue of formula (CT-I) and is covalently bound to the second of the three Xac1s, the second of the three Xac1s is covalently bound to the first of the three Xac1s and is covalently bound to the third of the three Xac1s, and the third of the three Xac1s is covalently bound to the second of the three Xac1s and is covalently bound to Z 4 Covalent bonding, If y=4, the first of the four Xac1 is covalently bound to the side chain amino functional group of the α-amino acid residue of formula (CT-I) and covalently bound to the second of the four Xac1, the second of the four Xac1 is covalently bound to the first of the four Xac1 and covalently bound to the third of the four Xac1, the third of the four Xac1 is covalently bound to the second of the four Xac1 and covalently bound to the fourth of the four Xac1, and the fourth of the four Xac1 is covalently bound to the third of the four Xac1 and covalently bound to Z 4 covalent binding; Z 4 Selected from H and a chelating agent; The condition is: if L 2 is a bond and CT is of formula (CT-II), wherein R CT1 is selected from H and CH3 and R CT2 is (C4-C6) alkyl, then Xaa10 may not be present; And wherein the compound of formula (I) may optionally contain a therapeutically active nuclide or a diagnostically active nuclide.

2. A compound of formula (I) or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, in X is selected from a bond and -CH2-; Z 1 Selected from chelating agents and NT; NT is selected from the group consisting of H, Ac, Hex, HPA, HO-succinyl, SaPr, Iva, HYDAc, Bio, nBuCAyl, AF488Ahx, and Hib; L 1 Selected from bonds and –(Xaa1) k – k is selected from 1, 2 and 3; in, If k = 1, then Xaa1 and Z 1 covalently bound to and covalently bound to Xaa2, If k=2, then the first of the two Xaa1 and Z 1 covalently bound to and covalently bound to the second of the two Xaa1s, and the second of the two Xaa1s is covalently bound to the first of the two Xaa1s and covalently bound to Xaa2, If k=3, then the first of the three Xaa1 and Z 1 covalently bound to and covalently bound to a second of the three Xaa1s, the second of the three Xaa1s is covalently bound to a first of the three Xaa1s and covalently bound to a third of the three Xaa1s, and the third of the three Xaa1s is covalently bound to a second of the three Xaa1s and covalently bound to Xaa2; Among them, when L 1 When Z is a key, 1 is NT; Xaa1 is each independently selected from Thr, Ala, Ser, Pamp, Leu, Ile, Nmt, Pamb, Ahx, APAc, PPAc, Bal, Cmp, Pab, O2Oc, Met and Ttds; Xaa2 is selected from the group consisting of Aib, Ala, Amd, Ams, amd, ams, Deg, Nmg, Pam and Pro; provided that when L 1 Xaa2 may not be present when it is a bond and NT is Hib; Xaa3 is selected from Phe, Nmf, 1Ni, 2Ni, 6Clw, Cys(Bzl), Hfe, Trp, Mpa, Opa and Ppa, wherein Phe, Nmf and Hfe are optionally substituted with 1 or 2 substituents independently selected from halogen, CH3, CN, CF3 and OH; Xaa5 is selected from the group consisting of Formula (Va), Formula (Vb), Hgn, Lys, Nle, Tap, Aph and Gln: Where R 5a Selected from H, (C1-C6) alkyl, Ac, C(=NR 5d )NR 5e R 5f and Bio; R 5d is selected from H and CH3; R 5e and R 5f Independently selected from H and (C1-C6)alkyl; R 5b is selected from H and (C1-C6)alkyl; R 5c is selected from H and CH3; m is selected from 2, 3, 4 and 5; and R 5g , R 5h and R 5i Independently selected from (C1-C6)alkyl; Xaa6 is selected from Formula (VI), Formula (VII), Nle and arg: Where R 6a Selected from H, C(=NR 6e )NR 6f R 6g 、C(=O)R 6h and pyridyl; R 6e is selected from H and CH3; R 6f Selected from H, (C1-C6) alkyl, Ac, NO2 and C(=O)NR 6i R 6j ; R 6i and R 6j independently selected from H and (C1-C2)alkyl; R 6g is selected from H and (C1-C6)alkyl; Or, R 6e and R 6f They can form a 5- or 6-membered heterocyclic ring. R 6h Selected from (C1-C6) alkyl, NR 6k R 6m and NR 6n C(=NR 6p )NR 6q R 6r ; R 6k and R 6m Independently selected from H and (C1-C6)alkyl; R 6n and R 6p Independently selected from H and CH3; R 6q and R 6r Independently selected from H and (C1-C6)alkyl; R 6b is selected from H and (C1-C6)alkyl; R 6c is selected from H and CH3; n is selected from 1, 2, 3 and 4; R 6d Selected from NR 6s C(=NR 6t )NR 6u R 6v , OH and NR 6w R 6x ; R 6s and R 6t Independently selected from H and CH3; R 6u , R 6v , R 6w and R 6x are independently selected from H and (C1-C6)alkyl; and q is selected from 2, 3 and 4; Xaa7 is selected from Formula (VIII), Formula (IX), Formula (X), Formula (XI), Dtc and Oic: Where R 7a Selected from H, (C1-C6) alkyl and (CH2) t R 7g ; R 7g Selected from OH, CO2H and NR 7h R 7i ; R 7h and R 7i Independently selected from H and (C1-C6)alkyl; t is selected from 1, 2, 3 and 4; R 7b is selected from H and (C1-C6)alkyl; Or, R 7a and R 7b They may form a 5- or 6-membered carbocyclic or heterocyclic ring. R 7c is selected from H and CH3; R 7d is selected from H, F and OH; R 7e Selected from H and F; R 7f is selected from H and CH3; u is selected from 2, 3 and 4; L 3 Selected from bonds and -(Xab1) v ; v is selected from 1, 2 and 3; Xab1 is each independently selected from Ttds, Pamb, APAc, O2Oc, Ahx, Pab and Cmp; If v = 1, then Xab1 and Z 3 covalently bonded to the side chain amino functional group of formula (X) or formula (XI), If v=2, then the first of the two Xab1 and Z 3 covalently bound to the second of the two Xab1, and the second of the two Xab1 is covalently bound to the first of the two Xab1 and covalently bound to the side chain amino functional group of formula (X) or formula (XI), If v=3, then the first of the three Xab1 and Z 3 covalently bound to the second of the three Xab1s, and the second of the three Xab1s is covalently bound to the first of the two Xab1s and is covalently bound to the third of the three Xab1s, and the third of the three Xab1s is covalently bound to the second of the three Xab1s and is covalently bound to the side chain amino functional group of formula (X) or formula (XI); Z 3 Selected from H and a chelating agent; Xaa8 is an α-amino acid residue, wherein the α-nitrogen atom of Xaa8 is unsubstituted or optionally substituted with CH3; Xaa10 is formula (XII) in R 10a Selected from (C1-C6) alkyl; R 10b is selected from H and CH3; R 10c is selected from H and CH3; L 2 Selected from: bond and -Xaa11-(Xaa12) s -, so that Xaa11 and Xaa10 are covalently bound; Xaa11 is selected from Thr, Ala, Bal, Gab, Gln, Glu, Gly, Leu, Nmt, Phe, Pro and Trp; s is selected from 0, 1, 2, 3, 4 and 5; and Xaa12 is each independently selected from Asp, asp, Ala, Gab, Ttds, Pamb, Cmp, O2Oc, APAc, Gly, Ser, Lys(Bio) and Pab; If s = 0, then Xaa11 and Z 2 Covalent bonding, If s = 1, Xaa12 is covalently bound to Xaa11 and to Z 2 Covalent bonding, If s=2, the first of the two Xaa12 is covalently bound to Xaa11 and covalently bound to the second of the two Xaa12, and the second of the two Xaa12 is covalently bound to the first of the two Xaa12 and covalently bound to Z. 2 Covalent bonding, If s=3, the first of the three Xaa12 is covalently bound to Xaa11 and covalently bound to the second of the three Xaa12, the second of the three Xaa12 is covalently bound to the first of the three Xaa12 and covalently bound to the third of the three Xaa12, and the third of the three Xaa12 is covalently bound to the second of the three Xaa12 and covalently bound to Z. 2 Covalent bonding, If s=4, the first of the four Xaa12 is covalently bound to Xaa11 and covalently bound to the second of the four Xaa12, the second of the four Xaa12 is covalently bound to the first of the four Xaa12 and covalently bound to the third of the four Xaa12, the third of the four Xaa12 is covalently bound to the second of the four Xaa12 and covalently bound to the fourth of the four Xaa12, and the fourth of the four Xaa12 is covalently bound to the third of the four Xaa12 and covalently bound to Z. 2 Covalent bonding, If s=5, the first of the five Xaa12s is covalently bound to Xaa11 and to the second of the five Xaa12s, the second of the five Xaa12s is covalently bound to the first of the five Xaa12s and to the third of the five Xaa12s, the third of the five Xaa12s is covalently bound to the second of the five Xaa12s and to the fourth of the five Xaa12s, the fourth of the five Xaa12s is covalently bound to the third of the five Xaa12s and to the fifth of the five Xaa12s, and the fifth of the five Xaa12s is covalently bound to the fourth of the five Xaa12s and to Z. 2 covalent binding; Z 2 Selected from CT, -en-chelating agent, -Ape-chelating agent and formula (CT-I) CT is selected from NH2, en, en(Me)2, en(Me), NHBu, NHnPen, AF488N3K-NH2, OH and Throl-OH; w is selected from 2, 3 and 4; L 4 is selected from the group consisting of a bond, Ttds, Pamb, APAc, O2Oc, Ahx, Pab and Cmp; Z 4 It is a chelating agent; The condition is: if L 2 is a bond and CT is NHnPen, then Xaa10 may not exist; And wherein the compound of formula (I) may optionally contain a therapeutically active nuclide or a diagnostically active nuclide.

3. The compound according to any one of claims 1 and 2, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein Z 1 , Z 2 , Z 3 and Z 4 Only 1 of the 10 contains a chelating agent.

4. The compound of any one of claims 1, 2 and 3, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein Z 2 is CT: and Xaa7 is selected from Formula (VIII), Formula (IX), Dtc and Oic.

5. The compound of claim 4 or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein Z 1 It is a chelating agent.

6. The compound according to any one of claims 4 and 5, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein L 1 -(Xaa1) k -; and wherein k is selected from 1 and 2.

7. The compound of any one of claims 4, 5 and 6, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein k is 2, and L 1 Formula (XIII): Among them, Xaa1 a Covalently bound to Xaa2; Xaa1 a is selected from Thr, Ile and Leu; and Xaa1 b Selected from Cmp, Ttds, Pamb, Ahx, APAc, Bal, O2Oc and Pab.

8. The compound of any one of claims 4, 5 and 6, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein k is 1 and Xaa1 is selected from Pamb, Bal, Cmp, Pab, Ahx, APAc, Thr, Pamp and PPAc.

9. The compound of any one of claims 4, 5, 6, 7 and 8, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein L2 is selected from a bond and -Xaa11-(Xaa12)s-; and s is selected from 0 and 1.

10. The compound of claim 9 or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein L 2 -Xaa11-(Xaa12) s -; s is selected from 0 and 1; and Xaa11 is selected from the group consisting of Thr, Bal, Gln, Phe, Gab, Nmt, Gly, Leu, Trp, Glu and Pro.

11. The compound of claim 10, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein s is 0.

12. The compound according to any one of claims 9 and 10, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein s is 1; and Xaa12 is Asp.

13. The compound of claim 9 or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein L 2 is the key.

14. The compound of any one of claims 9, 10, 11, 12 and 13, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein CT is selected from NH2, en, en(Me), en(Me)2, NHBu, Throl-OH and OH.

15. The compound of any one of claims 4, 5, 6, 7, 8 and 9, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein L 2 -Z 2 Selected from Thr-NH2, Bal-NH2, Glu-NH2, Pro-NH2, Gln-NH2, Trp-NH2, Leu-NH2, Gly-NH2 and Nmt-NH2.

16. The compound of any one of claims 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and 15, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein Xaa7 is selected from Formula (VIII), Formula (IX), Dtc and Oic, wherein R 7a Selected from H, (C1-C6) alkyl and (CH2) t R 7g ; t is selected from 1 and 2; and R 7g is selected from OH, CO2H and NH2, Preferably, Xaa7 is selected from Aib, Ala, Glu, Pro, Dfp, glu, Amd, 4Tfp, Pam, Deg, Nmg, Ams, ams, amd, Dtc and Oic, or Preferably, Xaa7 is selected from formula (VIII), and wherein R 7a is selected from the group consisting of H, (C1-C2)alkyl, CH2OH, CH2CO2H and CH2CH2CO2H; R 7b is selected from H and (C1-C2)alkyl; and R 7c It is H; more preferably, wherein Xaa7 is selected from Aib and Ala.

17. The compound of any one of claims 1, 2 and 3, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein Z 1 is NT, and Xaa7 is selected from Formula (VIII), Formula (IX), Dtc and Oic.

18. The compound of claim 17 or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein Z 2 is selected from en-chelating agents, -Ape-chelating agents and formula (CT-I), wherein if Z 2 For formula (CT-I), then Z 4 As a chelating agent.

19. The compound of any one of claims 17 and 18, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein L 1 Selected from bonds and (Xaa1) k ;and k is selected from 1 and 2.

20. The compound of claim 19 or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein k is 2 and L 1 Formula (XIII) Among them, Xaa1 a covalently bound to Xaa2 of formula (I); Xaa1 a is Thr; and Xaa1 b It is Met or Cmp.

21. The compound of claim 20 or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein Xaa1 b It's Met.

22. The compound of any one of claims 20 and 21, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein NT is selected from H, Ac and nBuCAyl.

23. The compound of claim 19, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein k is 1, and Xaa1 is selected from Thr, Ala, Pamp and Ser.

24. The compound of claim 23, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein Xaa1 is selected from Thr and Pamp; and NT is selected from Ac, nBuCAyl and Hex.

25. The compound of claim 19 or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein L 1 is a bond, preferably, NT is selected from Ac, HPA, HYDAc, Iva, SaPr and HO-succinyl.

26. The compound of any one of claims 17, 18, 19, 20, 21, 22, 23, 24 and 25, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein L 2 Yes -Xaa11-(Xaa12) s -;and s is selected from 0, 1 and 2.

27. The compound of claim 26 or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein Z 2 It is formula (CT-I).

28. The compound according to any one of claims 26 and 27, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein Xaa11 is Thr.

29. The compound of any one of claims 26, 27 and 28, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein L 2 for a) -Xaa11-(Xaa12) s ; s is 1; and Xaa12 is selected from the group consisting of Asp, Cmp, Ttds, Pamb, O2Oc, APAc and Pab, or b) -Xaa11-(Xaa12) s ; and s is 2; and L 2 Has the following structure: -Xaa11-Xaa12 a -Xaa12 b -;in Xaa12 a is selected from the group consisting of Asp, Cmp, Ttds, Pamb, O2Oc, APAc and Pab; and Xaa12 b It's Ttds.

30. The compound of any one of claims 17, 18, 19, 20, 21, 22, 23, 24, 25 and 26, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Z 2 Selected from -en-chelators and -Ape-chelators.

31. The compound of claim 30, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein L 2 is a key or Xaa11, where if L 2 is Xaa11, then Xaa11 is preferably Thr.

32. The compound of any one of claims 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 and 31, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein Xaa7 is selected from Formula (VIII), Formula (IX), Dtc and Oic, wherein R 7a Selected from H, (C1-C6) alkyl and (CH2) t R 7g ; R 7g Selected from OH and CO2H; t is selected from 1 and 2; and R 7b is selected from H and (C1-C6)alkyl, Preferably, a) Xaa7 is selected from the group consisting of Aib, Ala, Glu, Pro, Dfp, glu, Amd, 4Tfp, Pam, Deg, Nmg, Ams, ams, amd, Dtc, and Oic; or b) Xaa7 is of formula (VIII), and wherein R 7a is selected from the group consisting of H, (C1-C2)alkyl, CH2OH, CH2CO2H and CH2CH2CO2H; R 7b is selected from H and (C1-C2)alkyl; and R 7c It's H.

33. The compound of claim 32, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein Xaa7 is selected from Ala and Aib.

34. The compound of claims 1, 2 and 3, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa7 is selected from formula (X) and formula (XI); Z 3 It is a chelating agent; Z 1 is NT; and Z 2 is CT.

35. The compound of claim 34 or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein L 1 Selected from bonds and -(Xaa1) k -; and k is 1, where if L 1 is Xaa1, then Xaa1 is preferably Thr.

36. The compound of any one of claims 34 and 35, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein NT is selected from Ac, SaPr, Iva and HPA.

37. The compound of any one of claims 34, 35 and 36, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein L 2 Selected from bonds and -Xaa11-(Xaa12) s -, wherein s is selected from 0 and 1; preferably, Xaa11 is selected from Thr, Gln, Phe, Gab, Nmt, Bal, Gly, Leu, Trp, Glu and Pro.

38. The compound of claim 37, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein CT is NH2.

39. The compound of any one of claims 34, 35, 36, 37 and 38, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein Xaa7 is selected from Lys and Apc, wherein the ε-nitrogen atom of Lys or the γ-nitrogen atom of Apc is linked to a chelator, wherein an optional linker is inserted between Apc or Lys and the chelator.

40. A compound according to any one of claims 34, 35, 36, 37, 38 and 39, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa7 is selected from Apc(DOTA), Lys(DOTAGA-O2Oc), Lys(DOTA-O2Oc), Lys(DOTA-Pab), Lys(DOTA-Ahx), Lys(DOTA-APAc), Lys(DOTA-Pamb), Lys(DOTA-Cmp), Lys(DOTA-Ttds), Lys(DOTA).

41. The compound of any one of claims 34, 35, 36, 37 and 38, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein Xaa7 is selected from formula (X), wherein u is 4; L 3 Yes - (Xab1) v -; v is 1; and Xab1 is selected from Ttds, Pamb, APAc, O2Oc, Ahx and Pab.

42. A compound of any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40 and 41, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein the chelating agent is selected from DOTA, DOTAGA, LSC, NOPO, PCTA, DOTAM, Macropa, Crown, NOTA and NODAGA.

43. A compound of any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 and 42, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa2 is selected from Aib, Ala, Ams, ams, Deg, Pam and Pro.

44. A compound of any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42 and 43, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein Xaa3 is selected from Phe, 1Ni, 2Ni, 6Clw, Cys(Bzl), Hfe and Trp, wherein Phe, Nmf and Hfe are optionally substituted with 1 or 2 substituents independently selected from Cl, CH3, F, CN, CF3 and OH; preferably, Xaa3 is selected from Phe and Pcf.

45. A compound of any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43 and 44, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein Xaa5 is selected from Formula (Va), Formula (Vb), Hgn and Nle, and R 5g , R 5h and R 5i Yes CH 3； Preferably, Xaa5 is selected from formula (Va), and R 5a Selected from H, CH3, Ac and C(=NR 5d )NR 5e R 5f ; R 5e and R 5f Independently selected from H and CH3; R 5b is H; R 5c is H; and m is selected from 3 and 4; More preferably, Xaa5 is selected from Lys, Lys(Me), Kip and KMe3.

46. ​​A compound of any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44 and 45, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa6 is selected from Formula (VI), Formula (VII) and Nle, Where R 6a Selected from H, C(=NR 6e )NR 6f R 6g and C(=O)R 6h ; R 6e is H; R 6f Selected from H, CH3, Ac, NO2 and C(=O)NR 6i R 6j ; R 6g is selected from H and CH3; R 6h is selected from the group consisting of CH3, NH2 and NHC(=NH)NH2; R 6b is H; R 6c is H; and R 6d Selected from NHC(=NH)NH2 and NH 2； Preferably, a) Xaa6 is selected from Arg, Arg(Me), Cit, Egd, RMe2a, RMe3, Nle, Gln, Lys(Ac), Hgn, Arg(EtCAyl), Urr, Arg(Ac), Gln(Gu), Orn, Har, RMe2 and Eew; or b) Xaa6 is of formula (VI), and wherein n is 3; R 6a is C(=NH)NHR 6f ;and R 6f Selected from H, Ac, NO2 and CH3.

47. The compound of claim 46, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein Xaa6 is selected from Arg, Arg(Me), Cit, Egd, RMe2a and RMe3.

48. A compound of any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46 and 47, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa8 is selected from Formula (XIV), Gly, Val, Met, He and Thr: Where R 8a is selected from H, OH, NH2, COOH, C(=O)NH2, NHC(=NH)NH2, (C1-C8)alkyl, aryl and heteroaryl; w is selected from 1, 2 and 3; and R 8b is selected from H and CH3; Preferably, R 8a is selected from OH, COOH, C(═O)NH2, phenyl, CH2NHC(═NH)NH2, indole and CH(CH3)2; and w is selected from 1 and 2.

49. The compound of claim 48, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa8 is selected from Asn, Trp, Phe, Arg, Ser, Gly, Leu, Asp, Nmn, Glu and Asn.

50. The compound of any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 and 49, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa10 is of formula (XII): in R 10b is selected from H and CH3; R 10c It is H; Preferably, Xaa10 is selected from Tle, Leu, Val, Npg and Ile.

51. A compound according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein the compound is a compound of formula (Ia).

52. The compound of claim 51 or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein Xaa3 is selected from Phe, 1Ni, 2Ni, 6Clw, Cys(Bzl), Hfe and Trp, wherein Phe, Nmf and Hfe are optionally substituted with 1 or 2 substituents independently selected from Cl, CH3, F, CN, CF3 and OH; preferably, Xaa3 is selected from Phe and Pcf.

53. The compound of any one of claims 51 and 52, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein Xaa10 is of formula (XII), wherein R 10b is selected from H and CH3; R 10c It is H; Preferably, Xaa10 is selected from the compound of formula (XIV) More preferably, R 10a Selected from C(CH3)3, CH2CH(CH3)2, CH(CH3)2, CH(CH3)2, CH(CH3)C2H5 and CH2C(CH3)3.

54. The compound of any one of claims 51, 52 and 53, or a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate or a hydrate thereof, wherein the compound is a compound of formula (Ib) Where R 3c is selected from the group consisting of H, Cl, CH3, F, CN, CF3 and OH; and R 3c At the meta-position or para-position of the benzene ring of formula (Ib).

55. A compound of any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16, or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate or hydrate thereof, wherein Xaa2 is Aib or Ala; Xaa3 is Phe or Pcf; Xaa5 is Lys(Me), Lys, Kip or KMe3; Xaa6 is Arg(Me), Arg, Egd, Cit, RMe2a or RMe3; Xaa7 is Aib or Ala; Xaa8 is Asn; and Xaa10 is Tle or Leu.

56. The compound of any one of claims 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32 and 33, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein Xaa2 is Aib or Ala; Xaa3 is Phe or Pcf; Xaa5 is Lys or Lys(Me); Xaa6 is Arg or Arg(Me); Xaa7 is Aib or Ala; Xaa8 is Ans; and Xaa10 is Tle or Leu.

57. The compound of claim 1 or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the compound is selected from the following compounds: DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0194); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-NH2(PSM-0433); DOTA-Cmp-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0492); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0178); Ac-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0179); Ac-Thr-Aib-Phe-[Cys-Lys-Gln-Ala-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0180); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Hyp-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0181); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-Ttds-Ttds-AF488N3K-NH2(PSM-0183); DOTA-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-NH2(PSM-0184); Ac-Pamp-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en-DOTA(PSM-0186); Ac-Thr-Deg-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0187); SaPr-Aib-Pcf-[Cys-Lys-Arg-Lys(DOTA-APAc)-Asn-Cys]-Tle-Thr-NH2(PSM-0188); Ac-Thr-Aib-Pcf-[Cys-Lys-Gln(Gu)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0189); Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-lys(DOTA-Cmp)-NH2(PSM-0190); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-APAc-lys(DOTA)-NH2(PSM-0191); DOTA-Ttds-Thr-Aib-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0193); Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Glu-Asn-Cys]-Nle-Thr-Asp-NH2(PSM-0197); DOTA-Cmp-Tle-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0198); DOTA-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en(PSM-0199); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg-Aib-Asn-Cys]-Tle-NH2(PSM-0200); DOTA-Pamb-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0202); DOTA-Cmp-Thr-Aib-Pcf-[Cys-KMe2-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0203); nBuCAyl-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0204); Ac-Thr-Aib-Pcf-[Cys-Nle-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0205); nBuCAyl-Thr-Aib-Mcf-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0207); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-NHnPen(PSM-0208); DOTA-Bal-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0209); Ac-Thr-Aib-Phe-[Cys-Gln-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0210); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Lys(DOTA-Pab)-Asn-Cys]-Tle-Thr-NH2(PSM-0211); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-AsP-Ttds-lys(DOTA)-NH2(PSM-0212); SaPr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0215); DOTA-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Bal-NH2(PSM-0216); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Dfp-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-02l7); DOTAGA-Cmp-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0218); DOTA-Cmp-Leu-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0220); DOTA-Pamb-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en(PSM-0221); DOTA-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en(PSM-0222); DOTA-Cmp-Aib-Pcf-[Cys-Lys-Arg(Ac)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0223); SaPr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0224); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Har-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0225); H-Met-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Leu-Thr-Asp-Gly-Ser-Ttds-Ttds-Ttds-Lys(Bio)-NH2(PSM-0226); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-amd-Asn-Cys]-Tle-Thr-NH2(PSM-0227); Ac-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0228); Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Met-Cys]-Tle-Thr-NH2(PSM-0229); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-NH2(PSM-0230); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-Ttds-lys(DOTA)-NH2(PSM-0231); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Nmg-Asn-Cys]-Tle-Thr-NH2(PSM-0232); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Pam-Asn-Cys]-Tle-Thr-NH2(PSM-0233); DOTA-Ttds-Thr-Aib-Phe-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0234); Ac-Thr-Aib-Phe-[Cys-Lys-Nmr-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0235); Ac-Thr-Aib-Pcf-[Cys-Nle-Gln(Gu)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0236); DOTA-Ttds-Thr-Aib-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-NH2(PSM-0237); Ac-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Trp-Cys]-Tle-Thr-NH2(PSM-0238); Hex-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-lys(DOTA-Cmp)-NH2(PSM-0239); Ac-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Arg-Cys]-Tle-Thr-NH2(PSM-0240); DOTA-Cmp-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en(PSM-0241); Ac-Thr-Aib-Mcf-[Cys-Lys-Arg-Lys(DOTA-O2Oc)-Asn-Cys]-Tle-Thr-NH2(PSM-0243); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Kip-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0244); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Orn-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0245); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-ala-Asn-Cys]-Tle-Thr-NH2(PSM-0246); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-RMe2-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0247); DOTA-Cmp-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0248); Ac-Thr-Aib-lNi-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-AsP-NH2(PSM-0249); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Ttds-Ttds-Lys(Bio)-NH2(PSM-0250); DOTA-Ttds-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Leu-Thr-Asp-NH2(PSM-0251); Ac-Thr-Aib-Phe-[Cys-Lys-Cit-Aib-Asn-Cys],Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0252); Ac-Thr-Aib-Phe-[Cys-Lys-Glu-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0253); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Eew-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0254); DOTA-Cmp-Thr-Aib-Mpa-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0255); DOTA-Cmp-Thr-ams-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0256); DOTA-Cmp-Thr-Aib-Opa-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0257); nBuCAyl-Thr-Aib-Phe-[Cys-Lys-Opy-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0258); DOTA-Ttds-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0259); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-glu-Asn-Cys]-Tle-Thr-NH2(PSM-0260); DOTA-APAc-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0261); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Glu-NH2(PSM-0262); DOTA-APAc-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0263); Ac-Thr-Aib-Mtf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0264); Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-Ttds-lys(DOTA)-NH2(PSM-0266); HPA-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-lys(DOTA)-NH2(PSM-0267); Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en-DOTA(PSM-0269); DOTA-Pamb-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0270); AF488Ahx-Ttds-Ttds-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0272); DOTA-Pamb-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en(PSM-0273); DOTA-Cmp-Thr-Aib-Eaa-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0274); Ac-Thr-Aib-Mcf-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0275); Ac-Thr-Aib-Pnf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0278); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Ser-Cys]-Tle-Thr-NH2(PSM-0279); Ac-Thr-Aib-Phe-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0280); Ac-Aib-Pcf-[Cys-Lys-Arg-Lys(DOTA-APAc)-Asn-Cys]-Tle-Thr-NH2(PSM-0282); DOTA-Pamb-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0283); Ac-Thr-Aib-Mcf-[Cys-Lys-Cit-Lys(DOTA-O2Oc)-Asn-Cys]-Tle-Thr-NH2(PSM-0284); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Ttds-lys(DOTA)-NH2(PSM-0285); Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Thr-Asp-NH2(PSM-0287); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-lys(DOTA)-NH2(PSM-0288); Hex-Thr-Aib-Phe-[Cys-Lys-Gln-Aib-Asn-Cys]-Tle-Thr-Ttds-lys(DOTA)-NH2(PSM-0289); Iva-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-lys(DOTA)-NH2(PSM-0292); Ac-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Ser-Cys]-Tle-Thr-NH2(PSM-0293); Ac-Thr-Aib-Pff-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0294); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-Ttds-lys(DOTA)-NH2(PSM-0295); DOTA-Cmp-Thr-Aib-Mpa-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0296); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Gab-NH2(PSM-0297); Ac-Aib-Pcf-[Cys-Lys-Arg(Ac)-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0298); Ac-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Leu-Thr-Asp-Ttds-lys(DOTA)-NH2(PSM-0299); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-OH(PSM-0300); Ac-Thr-Aib-Mcf-[Cys-Lys-Arg-Lys(DOTAGA-O2Oc)-Asn-Cys]-Tle-Thr-NH2(PSM-0301); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Amd-Asn-Cys]-Tle-Thr-NH2(PSM-0302); Ac-Thr-Aib-Phe-[Cys-Lys-Gln-Aib-Asn-Cys]-Tle-Thr-Ttds-lys(DOTA)-NH2(PSM-0303); DOTA-Cmp-Thr-Aib-6Clw-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0304); DOTA-Ttds-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Leu-Thr-NH2(PSM-0305); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en(Me)2(PSM-0306); Ac-Thr-Aib-Phe-[Cys-Lys-Cit-Ala-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0307); DOTA-Cmp-Thr-Aib-5Clw-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0308); DOTA-Ahx-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0310); Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Thr-Gab-OH(PSM-0313); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-ams-Asn-Cys]-Tle-Thr-NH2(PSM-0314); Ac-Thr-Aib-Phe-[Cys-Lys-arg-Ala-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0315); DOTA-Pab-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0316); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Har-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0317); Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0318); Ac-Thr-Ala-Nmf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0319); Ac-Aib-Pcf-[Cys-Lys-Arg(Me)-Aib-Asn-Cys]-Tle-en-DOTA (PSM-0320); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Apc(DOTA)-Asn-Cys]-Tle-Thr-NH2 (PSM-0321); Ac-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-lys(DOTA-Cmp)-NH2 (PSM-0322); HPA-Aib-Pcf-[Cys-Lys-Arg-Lys(DOTA-APAc)-Asn-Cys]-Tle-Thr-NH2 (PSM-0324); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Lys(DOTA)-Asn-Cys]-Tle-Thr-NH2 (PSM-0326); SaPr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-lys(DOTA)-NH2 (PSM-0328); Ac-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2 (PSM-0329); Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Leu-Thr-Asp-Ttds-lys(DOTA)-NH2 (PSM-0330); DOTA-Cmp-Thr-Aib-Pcf-[Smc-Lys-Arg-Aib-Asn-Cys]-Tle-NH2 (or: DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Smc]-Tle-NH2) (PSM-0332); Ac-Thr-Aib-Phe-[Cys-Lys-Gln-Aib-Asn-Cys]-Tle-Thr-Asp-NH2 (PSM-0334); Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Ala-Cys]-Nle-Thr-Asp-NH2 (PSM-0335); Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0336); Ac-Thr-Aib-Pcf-[Cys-Lys-Nle-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0338); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTAGA)-NH2(PSM-0339); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Nmr-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0340); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Lys(Ac)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0341); DOTA-Ttds-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0342); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg(Me)-Aib-Asn-Cys]-Tle-NH2(PSM-0345); DOTA-Cmp-Thr-Amd-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0346); Ac-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0349); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-leu-Thr-NH2(PSM-0350); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0351); DOTA-Bal-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0352); Iva-Aib-Pcf-[Cys-Lys-Arg-Lys(DOTA-APAc)-Asn-Cys]-Tle-Thr-NH2(PSM-0353); DOTA-Cmp-Thr-Aib-Mcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-NH2(PSM-0354); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-RMe3-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0355); DOTA-Cmp-Ile-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0357); DOTA-Cmp-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-NH2(PSM-0361); Ac-Thr-Aib-Phe-[Cys-Lys-Glu-Ala-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0363); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0365); DOTA-Cmp-Thr-amd-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0366); Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-NH2(PSM-0367); DOTA-Ahx-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0368); DOTA-Cmp-Thr-Ams-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0369); Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Lys(DOTA-O2Oc)-Asn-Cys]-Tle-Thr-NH2(PSM-0370); nBuCAyl-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0371); Ac-Thr-Aib-Pmf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0372); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0374); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Deg-Asn-Cys]-Tle-Thr-NH2(PSM-0375); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Trp-NH2(PSM-0376); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Val-Nmt-NH2(PSM-0377); H-Cmp-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-CmP-lys(DOTA)-NH2(PSM-0378); Ac-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en-DOTA(PSM-0379); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-NH2(PSM-0380); DOTA-Pamb-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-NH2(PSM-0381); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Ams-Asn-Cys]-Tle-Thr-NH2(PSM-0382); Ac-Thr-Aib-Mcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0383); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en(PSM-0384); Ac-Thr-Aib-Phe-[Cys-Lys-Gln-Lys(DOTA)-Asn-Cys]-Tle-Thr-NH2(PSM-0385); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Pro-NH2(PSM-0388); Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Thr-asp-NH2(PSM-0389); DOTA-Cmp-Thr-Aib-6Clw-[Cys-Lys(Me)-A侣(Me)-Aib-Asn-Cys]-Tle-NH2(PSM-0390); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Ape-DOTA(PSM-0391); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-4Tfp-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0392); Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en(PSM-0393); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Aib-Thr-NH2 (PSM-0394); DOTA-Cmp-Thr-Aib-Pff-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-NH2 (PSM-0395); DOTA-Cmp-Thr-Aib-Mtf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-NH2 (PSM-0396); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Lys(DOTA)-Asn-Cys]-Tle-Thr-Asp-NH2 (PSM-0397); DOTA-Ttds-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2 (PSM-0398); Hex-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-lys(DOTA-Cmp)-NH2 (PSM-0400); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Lys(DOTA-O2Oc)-Asn-Cys]-Tle-Thr-NH2 (PSM-0401); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-asn-Cys]-Tle-Thr-NH2 (PSM-0402); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Oic-Asn-Cys]-Tle-Thr-Asp-NH2 (PSM-0403); Ac-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-lys(DOTA)-NH2 (PSM-0404); Hex-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Leu-Thr-Asp-Ttds-lys(DOTA)-NH2 (PSM-0405); DOTA-Cmp-Thr-Ams-Pcf-[Cys-Lys-A侣-Ams-Asn-Cys]-Tle-Thr-NH2 (PSM-0407); Ac-Thr-Nmg-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0408); DOTA-Cmp-Thr-Aib-Opa-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-NH2 (PSM-0409); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-04l0); Ac-Thr-Aib-Hfe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0411); Ac-Thr-Aib-Mmf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0412); DOTA-PPAc-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0413); Ac-Thr-Ala-Amf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0414); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Lys(DOTA-Cmp)-Asn-Cys]-Tle-Thr-NH2 (PSM-0415); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Glu-Asn-Cys]-Tle-Thr-NH2 (PSM-0416); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Lys(DOTA-Pamb)-Asn-Cys]-Tle-Thr-NH2 (PSM-0419); DOTA-Cmp-Thr-Aib-Pcf-[Smc-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-NH2 (or: DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Smc]-Tle-NH2) (PSM-0420); Ac-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Asn-Cys]-leu-Thr-NH2 (PSM-0421); Ac-Thr-Aib-Phe-[Cys-Tap-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-NH2 (PSM-0422); Ac-Thr-Aib-Phe-[Cys-Lys-Gln-Lys(DOTA-Ttds)-Asn-Cys]-Tle-Thr-NH2 (PSM-0423); Ac-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-NH2 (PSM-0424); Hex-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-Ttds-lys(DOTA)-NH2(PSM-0425); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Bal-NH2(PSM-0426); nBuCAyl-Thr-Aib-Pcf-[Cys-Lys-Opy-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0427); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0428); DOTA-Cmp-Thr-Aib-Mcf-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0431); DOTA-Pamb-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Bal-NH2(PSM-0432); nBuCAyl-Thr-Aib-Phe-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0434); Ac-Thr-Aib-Phe-[Cys-Gln-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0435); DOTA-Bal-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0437); Ac-Thr-Aib-Phe-[Cys-Aph-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0439); Ac-Thr-Aib-Cys(Bzl)-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0441); Ac-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0442); Ac-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-NH2(PSM-0443); Iva-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-lys(DOTA)-NH2(PSM-0444); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0445); DOTA-Pab-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0448); DOTA-Cmp-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Bal-NH2(PSM-0449); Iva-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0450); Ac-Thr-Aib-Phe-[Cys-Nmk-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0451); nBuCAyl-Thr-Aib-Pcr-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-lys(DOTA-Cmp)-NH2(PSM-0452); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Leu-NH2(PSM-0453); DOTA-Cmp-Thr-Aib-Ppa-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0454); DOTA-Cmp-Nmt-Ala-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0455); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en(Me)(PSM-0456); DOTA-Pamb-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-NH2(PSM-0458); DOTA-Cmp-Thr-Aib-Mnf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-NH2(PSM-0459); Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Pro-Asn-Cys]-Nle-Thr-Asp-NH2(PSM-0460); Hib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0461); Hex-Thr-Aib-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-Ttds-lys(DOTA)-NH2(PSM-0462); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Lys(DOTA-APAc)-Asn-Cys]-Tle-Thr-NH2(PSM-0464); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Lys(DOTA-Ttds)-Asn-Cys]-Tle-Thr-NH2(PSM-0465); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Ac)-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0466); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Bal-NH2(PSM-0467); Ac-Ser-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Thr-Asp-NH2(PSM-0469); nBuCAyl-Thr-Aib-Mcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0470); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Pab-lys(DOTA)-NH2(PSM-0471); Ac-Aib-Pcf-[Cys-Lys(Me)-Aib-Aib-Asn-Cys]-Tle-en-DOTA(PSM-0472); Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Ala-Asp-NH2(PSM-0476); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Gly-NH2(PSM-0477); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asp-Cys]-Tle-Thr-NH2(PSM-0478); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Gly-Cys]-Tle-Thr-NH2(PSM-0479); DOTA-Ttds-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Leu-NH2(PSM-0480); Ac-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-en-DOTA(PSM-0481); Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0482); DOTA-Cmp-Thr-Aib-Pcf-[Cys-KMe3-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0483); nBuCAyl-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0484); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Hgn-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0485); Ac-Thr-Aib-Mcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0486); Ac-Thr-Aib-Tyr-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0488); DOTA-Cmp-Aib-Pcf-[Cys-Lys-Gln(Gu)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0489); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Bio)-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0490); Ac-Ala-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Thr-Asp-NH2(PSM-0491); Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-OH(PSM-0493); Ac-Aib-Pcf-[Cys-Lys-Gln(Gu)-Aib-Asn-Cys]-Tle-Thr-CmP-lys(DOTA)-NH2(PSM-0494); Crown-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0495); Ac-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Glu-Cys]-Tle-Thr-NH2(PSM-0496); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Nml-Thr-NH2(PSM-0497); H-Met-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Leu-Thr-Asp-Gly-Ser-NH2(PSM-0498); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Egd-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0499); nBuCAyl-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-lys(DOTA-Cmp)-NH2(PSM-0500); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Thr-Asp-NH2(PSM-0501); Hex-Thr-Aib-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-Ttds-lys(DOTA)-NH2(PSM-0502); DOTA-Cmp-Thr-Aib-Mmf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-NH2(PSM-0503); DOTA-Ttds-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Thr-Asp-NH2(PSM-0504); DOTA-O2Oc-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0505); Ac-Aib-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0506); DOTA-Cmp-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0507); Ac-Thr-Pam-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0508); HPA-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2(PSM-0509); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-NHBu(PSM-0510); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Orn-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0511); DOTA-Cmp-Thr-Aib-Opa-[Cys-Lys-Cit-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0512); DOTA-Ahx-Aib-Phe-[Cys-Lys-Aib-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0513); Ac-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Bal-NH2(PSM-0514); Macropa-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0515); Ac-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-en-DOTA(PSM-0516); Ac-Thr-Aib-2Ni-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0517); HYDAc-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0518); DOTA-Ttds-Thr-Aib-Phe-[Cys-Lys-Gln-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0521); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Pamb-lys(DOTA)-NH2(PSM-0522); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-O2Oc-lys(DOTA)-NH2(PSM-0529); HPA-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0530); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Hgn-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0531); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Dtc-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0532); Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Thr-Asp-Ttds-lys(DOTA)-NH2(PSM-0533); DOTA-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-NH2(PSM-0534); Ac-Thr-Aib-Phe-[Cys-lys-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0535); DOTA-Cmp-Tle-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0538); DOTA-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Bal-NH2(PSM-0539); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Gln-NH2(PSM-0540); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Phe-Cys]-Tle-Thr-NH2(PSM-0541); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Lys(DOTA-Ttds)-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0542); DOTA-APAc-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0543); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Leu-Cys]-Tle-Thr-NH2(PSM-0545); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Urr-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0546); Ac-Thr-Pro-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Thr-Asp-NH2(PSM-0547); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Nmk-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0548); DOTA-Cmp-Thr-Aib-Ptf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-NH2(PSM-0549); Ac-Thr-Aib-Ptf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0550); Ac-Thr-Aib-Mff-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0551); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-NH2(PSM-0552); DOTA-CmP-Thr-Aib-Mff-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-NH2(PSM-0553); Ac-Thr-Aib-Pcr-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Throl-OH(PSM-0554); Ac-Thr-Aib-Mnf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0555); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Phe-NH2(PSM-0556); Ac-Thr-Aib-Ocf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0558); Ac-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2(PSM-0559); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Npg-NH2(PSM-0560); Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Nle-Thr-Ala-NH2(PSM-0562); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Glu-Cys]-Tle-Thr-NH2(PSM-0563); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-NH2(PSM-0565); Ac-Thr-Aib-Phe-[Smc-Lys-Arg-Ala-Asn-Cys]-Tle-Thr-Asp-NH2 (or: Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Ala-Asn-Smc]-Tle-Thr-Asp-NH2) (PSM-0567); Hex-Thr-Ala-Phe-[Cys-Lys-Arg-Ala-Asn-Cysr-Tle-Thr-Asp-Ttds-lys(DOTA)-NH2 (PSM-0568); Ac-Thr-Aib-Pcf-[Cys-Lys-Arg(Ac)-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0569); Ac-Thr-Aib-Pcf-[Cys-Nle-Arg(Ac)-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0570); nBuCAyl-Thr-Aib-Mcf-[Cys-Lys-Opy-Aib-Asn-Cys]-Tle-Thr-Cmp-lys(DOTA)-NH2 (PSM-0571); DOTA-Thr-Aib-Pcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0573); DOTA-Pamb-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Bal-NH2 (PSM-0574); Bio-Ttds-Ttds-Thr-Aib-Pcf-[Cys-Lys-A侣-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0575); Hex-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Ttds-lys(DOTA)-NH2 (PSM-0576); HO-Succinyl-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0577); Ac-Thr-Ala-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Nle-Thr-Asp-NH2 (PSM-0578); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg(EtCAyl)-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0579); DOTA-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0580); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Lys(DOTA-Ahx)-Asn-Cys]-Tle-Thr-NH2 (PSM-0582); DOTA-Cmp-Thr-Aib-Mcf-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0583); Ac-Thr-Aib-Pcf-[Cys-Lys-Cit-Aib-Leu-Cys]-Tle-Thr-NH2 (PSM-0584); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys-Arg-Ala-Nmn-Cys]-Tle-Thr-NH2 (PSM-0585); Ac-Thr-Aib-Trp-[Cys-Lys-Arg-Aib-Asn-Cys]-Tle-Thr-Asp-NH2 (PSM-0587); Ac-Thr-Aib-Phe-[Cys-Lys-Arg-Aib-Trp-Cys]-Tle-Thr-NH2 (PSM-0589); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-RMe2a-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0590): Macropa-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0591); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-RMel-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0592); DOTAM-Cmp-Thr-Aib-Pcf-[Cys-LysMe)-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0593); DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-OH (PSM-0594); LSC-Cmp-Thr-Aib-Pcff-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-Thr-NH2 (PSM-0601); DOTA-Cmp-Thr-Aib-Phe-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-en-H (PSM-0605) and DOTA-Cmp-Thr-Aib-Pcf-[Cys-Lys(Me)-Arg(Me)-Aib-Asn-Cys]-Tle-Bal-NH2 (PSM-0606).

58. A compound of any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56 and 57, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the compound comprises a diagnostically active nuclide or a therapeutically active nuclide.

59. The compound of claim 58 or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the compound comprises a diagnostically active nuclide; preferably, the diagnostically active nuclide is a diagnostically active radionuclide, more preferably, the diagnostically active radionuclide is selected from 43 Sc, 44 Sc, 51 Mn, 52 Mn, 64 Cu, 67 Ga, 68 Ga, 86 Y. 89 Zr, 94m Tc, 99m Tc, 111 In, 152 Tb, 155 Tb, 177 Lu, 201 Tl, 203 Pb, 18 F. 76 Br, 77 Br, 123 I. 124 I and 125 I.

60. A compound of any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56 and 57, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the compound comprises a therapeutically active nuclide; preferably, wherein the therapeutically active nuclide is a therapeutically active radionuclide; more preferably, the therapeutically active radionuclide is selected from 47 Sc, 67 Cu, 89 Sr. 90 Y. 111 In, 153 Sm, 149 Tb, 161 Tb, 177 Lu, 186 Re, 188 Re, 212 Pb, 212 Bi, 213 Bi, 223 Ra, 224 Ra, 225 Ac, 226 Th, 227 Th, 131 I and 211 At.

61. A compound of any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58 and 59, or a pharmaceutically acceptable salt, solvate or hydrate thereof, for use in a method of diagnosing a disease.

62. A compound of any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58 and 60, or a pharmaceutically acceptable salt, solvate or hydrate thereof, for use in a method of treating a disease.

63. A compound for use according to any one of claims 61 and 62, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the disease involves cells showing upregulated expression of prostate-specific membrane antigen (PSMA), preferably a diseased tissue comprising cells showing upregulated PSMA expression.

64. A compound for use according to any one of claims 61 and 62, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the disease is a tumor, preferably cancer or a tumor; more preferably, the tumor is selected from the group consisting of advanced tumors, metastatic tumors and primary tumors; most preferably, the tumor is selected from: a) prostate tumors, metastatic prostate tumors, lung tumors, kidney tumors, glioblastomas, pancreatic tumors, bladder tumors, sarcomas, melanomas, breast tumors, colon tumors, pheochromocytomas, esophageal tumors, stomach tumors, carcinomas, squamous cell carcinomas (e.g., endocervical, eyelid, conjunctival, vaginal, lung, oral, skin, bladder, tongue, larynx, and esophagus) and adenocarcinomas (e.g., prostate, small intestine, endometrium, endocervical, large intestine, lung, pancreas, esophagus, rectum, uterus, stomach, breast, and ovary), and combinations thereof, or b) prostate cancer (e.g. metastatic castration-resistant prostate cancer), kidney cancer (e.g. clear cell carcinoma), head cancer, neck cancer, head and neck cancer, lung cancer (e.g. non-small cell lung cancer), salivary gland cancer, breast cancer, colorectal cancer, esophageal cancer, stomach cancer, liver cancer (e.g. hepatocellular carcinoma), thyroid cancer, glioblastoma, glioma, gallbladder cancer, laryngeal cancer, leukemia / lymphoma, uterine cancer, skin cancer (e.g. melanoma), endocrine cancer, sarcoma, urethral cancer, pancreatic cancer, gastrointestinal cancer, ovarian cancer, cervical cancer, endometrial cancer, fallopian tube cancer, primary peritoneal cancer, blood cancer (e.g. diffuse large B-cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, follicular lymphoma, acute myeloid leukemia or multiple myeloma), cancer of unknown primary site, adenoma and tumor neovascularization.

65. A compound or a pharmaceutically acceptable salt, solvate or hydrate thereof for use according to any one of claims 61, 63 and 64, wherein the diagnostic method is an imaging method.

66. A compound of any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58 and 59, or a pharmaceutically acceptable salt, solvate or hydrate thereof, for use in a method of identifying a subject wherein the subject may or may not respond to treatment for a disease, wherein the method of identifying a subject The method comprises using a compound as described in any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58 and 59, or a pharmaceutically acceptable salt, solvate or hydrate thereof, for a diagnostic method, preferably for diagnosing a disease as described in any one of claims 61, 63, 64 and 65.

67. A compound of any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58 and 59, or a pharmaceutically acceptable salt, solvate or hydrate thereof, for use in a method of selecting a subject from a group of subjects, wherein the subject may or may not respond to treatment for a disease, wherein the compound is used to select a subject from a group of subjects. The method of selecting a subject comprises performing a diagnostic method using a compound of any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58 and 59, or a pharmaceutically acceptable salt, solvate or hydrate thereof, preferably for diagnosing a disease as described in any one of claims 61, 63, 64 and 65.

68. A compound of any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58 and 59, or a pharmaceutically acceptable salt, solvate or hydrate thereof, for use in a method of stratifying a group of subjects into subjects who are likely to respond to a treatment for a disease and subjects who are likely not to respond to a treatment for a disease, wherein the method for stratifying A method of stratifying a group of subjects comprising using a compound as described in any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58 and 59, or a pharmaceutically acceptable salt, solvate or hydrate thereof, for a diagnostic method, preferably for diagnosing a disease as described in any one of claims 61, 63, 64 and 65.

69. A compound for use according to any one of claims 66, 67 and 68, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the disease is a disease involving a prostate specific membrane antigen (PSMA) protein, or wherein the disease involves cells showing upregulated expression of a prostate specific membrane antigen (PSMA); preferably, the tumor is selected from a prostate tumor, a metastatic prostate tumor, a lung tumor, a kidney tumor, a glioblastoma, a pancreatic tumor, a bladder tumor, a sarcoma, a melanoma, a breast tumor, a colon tumor, a pheochromocytoma, an esophageal tumor, a gastric tumor, a carcinoma, a squamous cell carcinoma (e.g., cervical canal, eyelid, conjunctiva, vagina, lung, oral cavity, skin, bladder, tongue, larynx and esophagus) and adenocarcinoma (e.g., prostate, small intestine, endometrium, cervical canal, large intestine, lung, pancreas, esophagus, rectum, uterus, stomach, breast and ovary) and a combination thereof.

70. A compound of any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58 and 59, or a pharmaceutically acceptable salt, solvate or hydrate thereof, for use in a method of delivering a diagnostically active radionuclide or a therapeutically active radionuclide to prostate specific membrane antigen (PSMA); preferably, the diagnostically active radionuclide is selected from 43 Sc, 44 Sc, 51 Mn, 52 Mn, 64 Cu, 67 Ga, 68 Ga, 86 Y. 89 Zr, 94m Tc, 99m Tc, 111 In, 152 Tb, 155 Tb, 177 Lu, 201 Tl, 203 Pb, 18 F. 76 Br, 77 Br, 123 I. 124 I and 125 I, preferably selected from 18 F. 43 Sc, 44 Sc, 64 Cu, 67 Ga, 68 Ga, 86 Y. 89 Zr, 99m Tc, 111 In, 152 Tb, 155 Tb and 203 Pb, more preferably selected from 18 F. 64 Cu, 68 Ga and 111 In, and the therapeutically active radionuclide is selected from 47 Sc, 67 Cu, 89 Sr. 90 Y. 111 In, 153 Sm, 149 Tb, 161 Tb, 177 Lu, 186 Re, 188 Re, 212 Pb, 212 Bi, 213 Bi, 223 Ra, 224 Ra, 225 Ac, 226 Th, 227 Th, 131 I. 211 At is preferably selected from 47 Sc, 67 Cu, 90 Y. 161 Tb, 177 Lu, 188 Re, 212 Pb, 212 Bi, 213 Bi, 225 Ac, 227 Th is more preferably selected from 90 Y. 161 Tb, 177 Lu, 212 Pb, 225 Ac and 227 Th.

71. A compound for use according to claim 70, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein the prostate specific membrane antigen (PSMA) is expressed by cells, preferably prostate cells, metastatic prostate cells, lung cells, kidney cells, pancreatic cells, bladder cells, breast cells, colon cells, germ cells, esophageal cells, gastric cells, endothelial cells and combinations thereof, each of which shows upregulated PSMA expression.

72. A composition, preferably a pharmaceutical composition, wherein the composition comprises a compound according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58 and 60, or a pharmaceutically acceptable salt, solvate or hydrate thereof, and a pharmaceutically acceptable excipient.

73. A method for diagnosing a disease in a subject, wherein the method comprises administering to the subject a diagnostically effective amount of a compound according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58 and 59, or a pharmaceutically acceptable salt, solvate or hydrate thereof; preferably, the compound or a pharmaceutically acceptable salt, solvate or hydrate thereof comprises a diagnostically active nuclide, wherein the nuclide is preferably a diagnostically active radionuclide.

74. A method of treating a disease in a subject, wherein the method comprises administering to the subject a therapeutically effective amount of a compound according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58 and 60, or a pharmaceutically acceptable salt, solvate or hydrate thereof; preferably, the compound or a pharmaceutically acceptable salt, solvate or hydrate thereof comprises a therapeutically active nuclide, wherein the nuclide is preferably a therapeutically active radionuclide.

75. The method of any one of claims 73 and 74, wherein the disease is a disease involving the prostate specific membrane antigen (PSMA) protein; or the disease involves cells showing upregulated expression of prostate specific membrane antigen (PSMA), preferably a diseased tissue comprising cells showing upregulated expression of PSMA.

76. A kit comprising a compound according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59 and 60, or a pharmaceutically acceptable salt, solvate or hydrate thereof, one or more optional excipients and optionally one or more devices, wherein the device is selected from a labeling device, a purification device, a processing device, a radiation protection device, an analysis device or an administration device.

77. A kit according to claim 76 for use in any method as defined in any of the preceding claims.

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