Compounds containing fibroblast-activating protein ligands and their use

Abstract

The present invention provides compounds containing fibroblast-activating protein (FAP) ligands, methods for diagnosing diseases, methods for treating diseases, and methods for delivering effectors to FAP-expressing tissues. [Solution] The present invention relates to a compound comprising a cyclic peptide of formula (I) and an N-terminal modification group A attached to Xaa1, wherein each of Xaa1, Xaa2, Xaa3, Xaa4, Xaa5, Xaa6, and Xaa7, and any one thereof, are amino acid residues, and Yc has the structure of formula (X). TIFF2026062901000653.tif38135

Description

[Technical Field]

[0001] The present invention relates to compounds; inhibitors of fibroblast-activating protein (FAP); compositions comprising each compound and the inhibitor; compounds, inhibitors, and compositions for use in methods for diagnosing diseases; compounds, inhibitors, and compositions for use in methods for treating diseases; compounds, inhibitors, and compositions for use in methods for diagnosing and treating diseases, also known as "thera(g)nosis" or "thera(g)nostics"; compounds, inhibitors, and compositions for use in methods for delivering effectors to FAP-expressing tissues; methods for diagnosing diseases using each compound, inhibitor, and composition; methods for treating diseases using each compound, inhibitor, and composition; methods for diagnosing and treating diseases, also known as "thera(g)nosis" or "thera(g)nostics" using each compound, inhibitor, and composition; and methods for delivering effectors to FAP-expressing tissues using each compound, inhibitor, and composition. [Background technology]

[0002] Despite the increasing availability of treatment options, cancer remains the second leading cause of death worldwide. Treatment strategies primarily focus on targeting malignant cancer cells themselves, neglecting the constantly present surrounding tumor microenvironment (TME), which limits the access of therapeutic cancer cell therapies (Valkenburg et al., Nat Rev Clin Oncol, 2018, 15:366). The TME is part of the tumor mass and consists not only of a heterogeneous population of cancer cells but also of various resident and invasive host cells, secreted factors, and extracellular matrix proteins (Quail et al., Nat Med, 2013, 19:1423). The dominant cell type found in the TME is cancer-associated fibroblasts (CAFs) (Kalluri, Nat Rev Cancer, 2016, 16:582). For example, many different cell types, such as fibroblasts, mesenchymal stem cells, smooth muscle cells, epithelial cells, or endothelial cells, have been described as sources and origins for CAFs (Madar et al., Trends Mol Med, 2013, 19:447). CAFs often exhibit mesenchymal-like characteristics and are the dominant cell type within solid tumor masses. CAFs are attracting increasing attention as players in tumor progression and homeostasis (Gascard et al., Genes Dev, 2016, 30:1002; LeBleu et al., Dis Model Mech, 2018, 11).

[0003] In recent years, fibroblast-activating protein (FAP) has lost its reputation as a marker for carcinomatous fibroblast (CAF) (Shiga et al., Cancers (Basel), 2015, 7:2443; Pure et al., Oncogene, 2018, 37:4343; Jacob et al., Curr Mol Med, 2012, 12:1220). Due to the ubiquity of CAF in tumors and stroma, FAP has been found to be a suitable marker for radiopharmaceutical diagnostics and a suitable target for radiopharmaceutical therapy (Siveke, J Nucl Med, 2018, 59:1412).

[0004] Fibroblast-activating protein α (FAP) is a member of the type II transmembrane serine protease and S9 prolyl oligopeptidase family (Park et al., J Biol Chem, 1999, 274:36505). Its closest family member, DPP4, shares 53% homology with FAP. Like other DPP enzymes (DPP4, DPP7, DPP8, DPP9), FAP possesses post-proline exopeptidase activity. Furthermore, FAP, like prolyl oligopeptidase / endopeptidase (POP / PREP), possesses endopeptidase activity. The FAP gene is highly conserved across various species. The extracellular domain of human FAP has 90% amino acid sequence identity with mouse and rat FAP. Mouse FAP has 97% sequence identity with rat FAP.

[0005] Structurally, FAP is a 760-amino acid transmembrane protein consisting of a short N-terminal cytoplasmic tail (6 amino acids), a single transmembrane domain (20 amino acids), and an extracellular domain of 734 amino acids (Aertgeerts et al., J Biol Chem, 2005, 280:19441). This extracellular domain consists of an 8-blade β-propeller domain and an α / β-hydrolase domain. The three catalytic residues, Ser624, Asp702, and His734, are located at the interface between the β-propeller domain and the hydrolase domain. The active site is accessible through the central pore of the β-propeller domain or through a narrow cavity between the β-propeller domain and the hydrolase domain. FAP monomers are inactive, but they form active homodimers and heterodimers with DPP4 (Ghersi et al., Cancer Res, 2006, 66:4652). Soluble homodimer FAP has also been described (Keane et al., FEBS Open Bio, 2013, 4:43; Lee et al., Blood, 2006, 107:1397).

[0006] FAP possesses dual enzymatic activity (Hamson et al., Proteomics Clin Appl, 2014, 8:454). Its dipeptidyl peptidase activity cleaves the two amino acids at the N-terminus after the proline residue. FAP substrates rapidly cleaved by its dipeptidyl peptidase activity are neuropeptide Y, peptide YY, substance P, and type B natriuretic peptide. Collagen I and III, FGF21, and α2-antiplasmin have been shown to be cleaved by the endopeptidase activity of FAP. While FAP cannot cleave native collagen, pre-digestion by other proteases such as matrix metalloproteinases facilitates further collagen cleavage by FAP. Collagen processing may affect the migratory ability of cancer cells. In addition to increased invasiveness of cancer cells through extracellular matrix remodeling, several other FAP-mediated tumorigenic roles have been proposed, including increased proliferation and angiogenesis. Furthermore, stromal expression of FAP is associated with evading immune surveillance in various cancers, suggesting a role in antitumor immunity (Pure et al., Oncogene, 2018, 37:4343).

[0007] FAP is transiently expressed during normal development but is rarely expressed in healthy adult tissues. In transgenic mice, FAP has been shown to be expressed in adipose tissue, skeletal muscle, skin, bone, and pancreas (Pure et al., Oncogene, 2018, 37: 4343; Roberts et al., J Exp Med, 2013, 210: 1137). However, FAP knockout mice have a healthy phenotype, suggesting overlapping roles under normal conditions (Niedermeyer et al., Mol Cell Biol, 2000, 20: 1089). In sites of active tissue remodeling, including wound healing, fibrosis, arthritis, atherosclerosis, and cancer, FAP becomes highly upregulated in stromal cells (Pure et al., Oncogene, 2018, 37: 4343).

[0008] FAP expression in the tumor stroma of 90% of epithelial carcinomas was first reported in 1990 under the use of the monoclonal antibody F19 (Garin-Chesa et al., Proc Natl Acad Sci USA, 1990, 87:7235; Rettig et al., Cancer Res, 1993, 53:3327). Stromal cells expressing FAP were further characterized as cancer-associated fibroblasts (CAFs) and cancer-associated pericytes (Cremasco et al., Cancer Immunol Res, 2018, 6:1472). FAP expression on malignant epithelial cells has also been reported, but its significance has not yet been established (Pure et al., Oncogene, 2018, 37:4343). Busek et al. (Busek et al., Fron Table 1 below, taken from Biosci (Landmark Ed), 2018, 23:1933), summarizes the expression of FAP in various malignant tumors exhibiting different tumor types and cellular expression.

[0009] [Table 1-1]

[0010] [Table 1-2]

[0011] FAP expression in CAFs has been demonstrated in almost all carcinomas and sarcomas (Pure et al., Oncogene, 2018, 37:4343; Busek et al., Front Biosci (Landmark Ed), 2018, 23:1933). Furthermore, CAFs are present in hematological malignancies (Raffaghello et al., Oncotarget, 2015, 6:2589). Therefore, the use of FAP as a therapeutic target is not limited to any particular tumor entity.

[0012] The abundance of CAFs expressing FAP is reported to correlate with poor prognosis. Across various human tumor indications, FAP expression has been reported to correlate with higher tumor malignancy and worse overall survival (Pure et al., Oncogene, 2018, 37:4343).

[0013] As described above, FAP and FAP-expressing cells present in the tumor microenvironment have been shown to significantly influence tumor progression (Hanahan et al., Cancer Cell, 2012, 21:309). Furthermore, due to its relatively selective expression in tumors, FAP is, As described below, it is considered a suitable target for therapeutic and diagnostic agents (Siveke, J Nucl Med, 2018, 59:1412; Christiansen et al., Neoplasia, 2013, 15:348; Zi et al., Mol Med Rep, 2015, 11:3203).

[0014] Shortly after its discovery, FAP was utilized as a therapeutic target in cancer. To date, various strategies have been explored, including, for example, inhibition of FAP enzyme activity, removal of FAP-positive cells, or targeted delivery of cytotoxic compounds.

[0015] In 2007, talabostat (Val-boro-Pro, PT-100), an inhibitor of FAP and DPP4, was developed by Point Therapeutics (e.g., U.S. Patent No. 6,890,904, WO9916864). Pennisi et al. (Pennisi et al., Br J Haematol, 2009, 145:775) observed a reduction in tumor growth in several myeloma animal models and cancer syngeneic mouse models. Furthermore, several other prolylboronic acid derivatives have been developed, and F These derivatives were reported as putative selective inhibitors for AP. These derivatives exhibit instability in aqueous environments at physiological pH (Coutts et al., J Med Chem, 1996, 39:2087) and show nonspecific reactivity with other enzymes.

[0016] WO2008 / 116054 disclosed hexapeptide derivatives in which the compound contains a C-terminal bisamino or boronic acid functional group. US2017 / 0066800 disclosed pseudopeptide inhibitors, such as M83, that are effective against FAP. These inhibitors were evaluated in lung and colon cancer xenografts in immunodeficient mice. Suppression of tumor growth was observed (Jackson et al., Neoplasia, 2015, 17:43). These pseudopeptides inhibit the activity of both prolyl oligopeptidase (POP / PREP) and FAP, thereby ruling out their use as specific therapeutic FAP inhibitors.

[0017] US2008 / 280856 disclosed inhibitors based on nanomolar concentrations of boronic acid. The inhibitors exhibit bispecific inhibition of FAP and PREP, thereby excluding their use as specific therapeutic FAP inhibitors.

[0018] FAP inhibitors based on cyclic peptides have been disclosed, for example, in WO2016 / 146174 and WO2006 / 042282. WO2016 / 146174 discloses a peptide for the diagnosis and treatment of FAP-expressing tumors exhibiting specificity for FAP, the closely related homolog DPP4 was not recognized by the peptide. WO2006 / 042282 discloses a polypeptide for the treatment of melanoma. Inhibition of melanoma growth and metastasis was shown in nude mice.

[0019] WO99 / 75151 and WO01 / 68708 disclosed the humanized FAP monoclonal antibody, F19 (cibrotuzumab). Furthermore, the anti-FAP antibody F19 and its humanized version were disclosed in WO99 / 57151 and WO01 / 68708. The development methodology included, for example, the generation of high-affinity, species-cross-reactive, FAP-specific scFv converted to a divalent derivative (Brocks et al., Mol Med, 2001, 7:461). In Phase I and Phase II clinical trials, cibrotuzumab showed specific tumor enrichment, but failed to demonstrate measurable therapeutic activity in patients with metastatic colorectal cancer, with only 2 out of 17 patients having stable disease (Hofheinz et al., Onkologie, 2003, 26:44). This F19 antibody was shown not to block any cellular or protease function of FAP, which may explain the lack of therapeutic effect (Hofheinz et al., Onkologie, 2003, 26:44; Scott et al., Clin Cancer Res, 2003, 9:1639).

[0020] US2018 / 022822 disclosed novel molecules that specifically bind to human FAP and its epitopes as human-derived antibodies and chimeric antigen receptors (CARs) useful in treating FAP-induced diseases and conditions. Treatment of mice carrying orthotopic and syngeneic MC38 colorectal tumors with anti-FAP antibodies reduced tumor diameter and the number of metastases. WO2012 / 020006 disclosed glycosylated antibodies carrying modified oligosaccharides in their Fc regions. Subsequently, bispecific antibodies specific to FAP and DR5 were developed as the subject of WO2014 / 161845. These antibodies induced tumor cell apoptosis in in vitro and in vivo preclinical tumor models with FAP-positive stroma (Brunker et al., Mol Cancer Ther, 2016, 15:946). Antibody-drug conjugates and immunotoxins targeting FAP are described in WO2015 / 118030. In vitro toxicity and in vivo inhibition of tumor growth were demonstrated after application of the anti-hu / moFAP hu36:cytolysin ADC candidate. It is unclear whether these antibodies were able to inhibit FAP activity.

[0021] A small molecule FAP inhibitor based on (4-quinolinoyl)glycyrrhizin exhibiting low nanomolar inhibitory efficacy and high selectivity against related DPP and PREP was described by Jansen et al. (Jansen et al., J Med Chem, 2014, 57:3053; Jansen et al., ACS Med Chem Lett, 2013, 4:491) and disclosed in WO2013 / 107820. However, that compound is not structurally related to the compound of the present invention and contains a warhead that provides covalent bonding to FAP.

[0022] In recent years, several FAP-targeted radiopharmaceutical methods, as illustrated herein, have been developed. WO2010 / 036814 disclosed small molecule inhibitors of FAP for use as therapeutic agents by inhibiting FAP enzyme activity, or as radiopharmaceuticals by binding to FAP.

[0023] WO2019 / 083990 disclosed imaging and radiotherapeutic agents based on small molecule FAP inhibitors described by Jansen et al. (Jansen et al., J Med Chem, 2014, 57:3053; Jansen et al., ACS Med Chem Lett, 2013, 4:491). Furthermore, some authors also disclosed Jansen et al. (Jansen et al., J Med Chem, 2014, 57:3053; Jansen et al., ACS We have described the selective uptake of imaging and radiotherapy agents in tumors of cancer patients based on FAP inhibitors, as described by Med Chem Lett, 2013, 4:491 (Lindner et al., J Nucl Med, 2018, 59:1415; Loktev et al., J Nucl Med, 2018, 59:1423; Giesel et al., J Nucl Med, 2019, 60:386; Loktev et al., J Nucl Med, 2019, Mar 8 (preprint electronic edition); Giesel et al., Eur J Nucl Med Mol Imaging, 2019, 46:1754; Kratochwil et al., J Nucl Med, 2019, 60:801).

[0024] 131 Clinical evaluation of a humanized form of 1-labeled F19 antibody (cibrotuzumab) showed selective uptake by tumors rather than normal tissues in patients with colorectal cancer or non-small cell lung cancer (Scott et al., Clin Cancer Res, 2003, 9:1639). This may be due to the long circulation time of the antibody, which makes it unsuitable for diagnostic, therapeutic, or diagnostic-therapeutic techniques involving radionuclides.

[0025] WO2011 / 040972 disclosed a high-affinity antibody that recognizes both human and mouse FAP antigens as a potent radioactive immunoconjugate. ESC11 IgG1 induces downmodulation and internalization of surface FAP (Fischer et al., Clin Cancer Res, 2012, 18:6208). WO2017 / 211809 disclosed a tissue-targeted thorium-227 conjugate in which the targeting portion has specificity for FAP. However, the long circulation times of these antibodies make them unsuitable for diagnostic, therapeutic, or diagnostic-therapeutic techniques involving radionuclides.

[0026] FAP is also described as being involved in diseases other than tumor indications, examples of which are given below. Fibroblast-like synovial cells in the joints of patients with rheumatoid arthritis show significantly increased expression of FAP (Bauer et al., Arthritis Res Ther, 2006, 8:R171; Milner et al., Arthritis Res Ther, 2006, 8:R23). In rheumatoid arthritis, interstitial cells play a crucial role in organizing the structure of the synovial tissue of the joint by producing extracellular matrix components, recruiting infiltrating immune cells, and secreting inflammatory mediators. They play a role. There is considerable evidence supporting the role of these cells in driving inflammation and the persistence of joint damage (Bartok et al., Immunol Rev, 2010, 233:233; Turner et al., Curr Opin Rheumatol, 2015, 27:175). In rheumatoid arthritis, FAP has a pathological role in cartilage turnover, at least by promoting proteoglycan loss and subsequent chondrolysis (Bauer et al., Arthritis Res Ther, 2006, 8:R171; Waldele et al., Arthritis Res Ther, 2015, 17:12). Therefore, it may be useful as a marker for patient stratification or as a therapeutic target for evaluating and tracking the success of treatment (Bauer et al., Arthritis Res Ther, 2006, 8:R171). In mice, the treatment response is 99m This was demonstrated using SPECT / CT imaging with Tc-labeled anti-FAP antibody (van der Geest et al., Rheumatology (Oxford), 2018, 57:737; Laverman et al., J Nucl Med, 2015, 56:778; van der Geest et al., J Nucl Med, 2017, 58:151).

[0027] Furthermore, FAP has been recognized not only as a marker of activated fibroblasts in the injury response (Tillmanns et al., Int J Cardiol, 2013, 168:3926) but also as an important player in the wound healing process (Ramirez-Montagut et al., Oncogene, 2004, 23:5435). Jing et al. demonstrated the time-dependent course of changes in FAP expression after burn wounds in rats (Jing et al., Nan Fang Yi Ke Da Xue Xu Bao, 2013, 33:615). Inhibition of FAP activity in reactive wound fibroblasts in keloid scars, a common benign fibroproliferative reticular skin lesion, may offer a therapeutic option to prevent disease progression (Dienus et al., Arch Dermatol Res, 2010, 302:725).

[0028] Upregulated FAP expression has been observed in fibrosis, for example, in idiopathic pulmonary fibrosis, Crohn's disease, and hepatic fibrosis. Upregulated FAP expression was observed in an ex vivo model of Crohn's disease, a chronic inflammatory bowel disease characterized by excessive, misequilibrium extracellular matrix (ECM) deposition. FAP inhibition reconstituted extracellular matrix homeostasis (Truffi et al., Inflamm Bowel Dis, 2018, 24:332). Similar observations were made by Egger et al. (Egger et al., Eur J Pharmacol, 2017, 809:64) using a mouse model of pulmonary fibrosis. Inhibition of FAP results in a reduction of fibrous pathology. FAP is also expressed in tissue remodeling regions in chronically damaged liver (Wang et al., Front Biosci, 2008, 13:3168), and FAP expression by hepatic stellate cells correlates with the histological severity of liver disease (Gorrell et al., Adv Exp Med Biol, 2003, 524:235). Therefore, FAP is also a promising target in the treatment of hepatic fibrosis (Lay et al., Front Biosci(Landmark Ed),2019,24:1).

[0029] FAP is expressed in atherosclerotic lesions and is upregulated in activated vascular smooth muscle cells (Monslow et al., Circulation, 2013, 128:A17597). Monslow et al. showed that targeted inhibition of FAP in atherosclerotic lesions can reduce overall lesion volume, inhibit inflammatory cell homing, and increase lesion stability by altering lesion structure through its ability to prefer substrate-rich lesions over inflammation. More importantly, many atherosclerotic pathologies share a common pathological feature: rupture of atherosclerotic plaques that induce atherosclerotic lesions (Davies et al., Br Heart J, 1985, 53:363; Falk, Am J Cardiol, 1989, 63:114e). Rupture of the fibrous capsule in progressive atherosclerotic plaques is a significant trigger for acute coronary syndrome, which can lead to myocardial infarction and sudden cardiac death. Important events in promoting plaque instability One such mechanism is the breakdown of the fibrous capsule, which causes thrombosis and subsequent vascular occlusion by exposing the underlying thrombus-forming plaque core to blood flow (Farb et al., Circulation, 1996, 93:1354; Virmani et al., J Am Coll Cardiol, 2006, 47:C13). Brokopp et al. showed that FAP contributes to the breakdown of type I collagen in the fibrous capsule (Brokopp et al., Eur Heart J, 2011, 32:2713). Radiolabeled tracers have been developed and their applicability to atherosclerosis imaging has been demonstrated (Meletta et al., Molecules, 2015, 20:2081). [Modes for carrying out the invention]

[0030] A fundamental problem of the present invention is to provide a compound suitable as a diagnostic and / or therapeutic agent, particularly when conjugated to a diagnostic and / or therapeutically active effector. A further fundamental problem of the present invention is to provide a compound suitable as a diagnostic and / or therapeutic agent, particularly when conjugated to a diagnostic and / or therapeutically active effector, thereby the compound becoming a potent inhibitor of FAP activity, preferably with a pIC50 equal to or greater than 6.0. A further fundamental problem of the present invention is to provide a compound suitable as a diagnostic and / or therapeutic agent, particularly when conjugated to a diagnostic and / or therapeutically active effector, in the diagnosis and / or treatment of diseases in which affected cells and / or affected tissues express FAP. A further fundamental problem of the present invention is to provide a compound suitable for delivering a diagnostic and / or therapeutically effective agent to affected cells and / or affected tissues, more specifically to affected cells and / or affected tissues expressing FAP, preferably the affected tissues including or containing cancer-associated fibroblasts. Furthermore, an underlying problem of the present invention is to provide a method for diagnosing a disease, a method for treating and / or preventing a disease, and a method for a combination of diagnosing and treating a disease, preferably such a disease is one in which cells and / or tissues expressing FAP are involved, more specifically diseased cells and / or diseased tissues expressing FAP, preferably the diseased tissue includes or contains cancer-associated fibroblasts. A further underlying problem of the present invention is to provide a method for identifying subjects that are likely to respond to or not respond to treatment of a disease, and a method for selecting subjects that are likely to respond to or not respond to treatment of a disease from a group of subjects. Another underlying problem of the present invention is to provide a pharmaceutical composition comprising a compound having the features outlined above. Furthermore, an underlying problem of the present invention is to provide a kit suitable for use in any of the above methods.

[0031] There is a need for compounds suitable as diagnostic and / or therapeutic agents, particularly when conjugated to diagnostic and / or therapeutically active effectors. Furthermore, there is a need for compounds suitable as diagnostic and / or therapeutic agents, particularly when conjugated to diagnostic and / or therapeutically active effectors, thereby making the compound a potent inhibitor of FAP activity, preferably having a pIC50 equal to or greater than 6.0. Furthermore, there is a need for compounds suitable as diagnostic and / or therapeutic agents, particularly when conjugated to diagnostic and / or therapeutically active effectors, in the diagnosis and / or treatment of diseases in which affected cells and / or affected tissues express FAP. Furthermore, there is a need for compounds suitable for delivering diagnostic and / or therapeutically effective agents to affected cells and / or affected tissues, more specifically to affected cells and / or affected tissues expressing FAP, preferably in which the affected tissue contains or is composed of cancer-associated fibroblasts. Furthermore, methods for diagnosing a disease, methods for treating and / or preventing a disease, and methods for a combination of diagnosing and treating a disease, preferably such a disease is characterized by cells and / or tissues expressing FAP, more specifically by diseased cells expressing FAP There is a need for methods for diseases involving affected cells and / or diseased tissue, preferably in which the diseased tissue contains or comprises cancer-associated fibroblasts. Furthermore, there is a need for methods for identifying subjects likely to respond to or not respond to treatment of the disease, and for selecting subjects likely to respond to or not respond to treatment of the disease from a group of subjects. Furthermore, there is a need for pharmaceutical compositions comprising compounds having the features outlined above. Furthermore, there is a need for kits suitable for use in any of the above methods. The present invention satisfies these needs.

[0032] These and other issues are addressed by the subject matter of the attached claims. These and other problems underlying the present invention are also solved by the following embodiments. Embodiment 1. Formula (I)

[0033] [ka]

[0034] cyclic peptide and a compound comprising an N-terminal modification group A bonded to Xaa1, The aforementioned peptide sequence is drawn from left to right in the direction from the N-terminus to the C-terminus. Xaa1 is equation (II).

[0035] [ka]

[0036] It is a residue of the amino acid, R 1a is -NH-, R 1b is H or CH3, n=0 or 1, The aforementioned N-terminal modification group A is covalently bonded to the nitrogen atom of Xaa1, The carbonyl group of Xaa1 is covalently bonded to the nitrogen of Xaa2. The sulfur atom of Xaa1 is covalently bonded to Yc as a thioether. Xaa2 is equation (III), (IV), or (XX)

[0037] [ka]

[0038] It is a residue of the amino acid, R 2a , R 2b , R 2ceach independently selected from the group consisting of (C1-C2) alkyl and H, wherein the (C1-C2) alkyl may be substituted by a substituent selected from the group consisting of OH, NH2, halogen, and (C5-C7) cycloalkyl, p = 0, 1, or 2, v = 1 or 2, w = 1, 2, or 3, the amino acid of formula (IV) may be substituted by one or two substituents selected from the group consisting of methyl, OH, NH2, and F at the indicated ring positions 3 and 4, Xaa3 is a residue of an amino acid of formula (V) or (XX)

[0039]

Chemical formula

[0040] and X 3 is selected from the group consisting of CH2, CF2, CH-R 3b , S, O, and NH, p = 1 or 2, v = 1 or 2, w = 1, 2, or 3, R 3a is H, methyl, OH, NH2, or F, R 3b is methyl, OH, NH2, or F, Xaa4 is a residue of an amino acid of formula (VI)

[0041]

Chemical formula

[0042] and R 4a is selected from the group consisting of H, OH, COOH, CONH2, X 4 , and -NH-CO-X 4 , and X 4X is selected from the group consisting of (C1-C6) alkyl, (C5-C6) aryl, and (C5-C6) heteroaryl, 4 It may be substituted with one or two substituents selected from the group consisting of methyl, CONH2, halogen, NH2, and OH. q = 1, 2, or 3, and one or two hydrogens of the one, two, or three CH2- groups are optionally substituted individually with methyl, ethyl, (C5-C6)aryl, or (C5-C6)heteroaryl groups. R 4b is methyl or H, Xaa5 structure (VII)

[0043] [ka]

[0044] It is a residue of the amino acid, R 5 The group selected is from the OH and NH2 groups. r = 1, 2, or 3, Xaa6 is an amino acid selected from the group consisting of aromatic L-α-amino acids and heteroaromatic L-α-amino acids. Xaa7 is equation (IX).

[0045] [ka]

[0046] It is an aminothiol or amino acid residue, R 7a -CO-, -COOH, -CONH2, -CH2-OH, -(CO)-NH-R 7b ,-(CO)-(NR 7c )-R 7b , or H, R 7b and R 7c Each of them is independently a (C1-C4) alkyl, t is 1 or 2, Yc is given by equation (X).

[0047] [ka]

[0048] The structure is such that the sulfur atom of Xaa1 and the sulfur atom of Xaa7 are linked under the formation of two thioether linkages, thereby forming equation (XXI)

[0049] [ka]

[0050] It forms a ring structure, The substitution pattern of the aromatic group in formula (X) is ortho, meta, or para. n=0 or 1, t=1 or 2, Y 1 is CH or N, Y 2 is N or CR c1 And, R c1 is H or CH2-R c2 And, R c2 is equation (XI), (XII), or (XXII)

[0051] [ka]

[0052] It has the following structure: R c3 and R c4 Each is independently selected from the group consisting of H and (C1-C4) alkyl groups, u = 1, 2, 3, 4, 5, or 6, x and y are independently 1, 2, or 3. X = O or S In equations (XI) and (XXII), one of the nitrogen atoms is R c1It is bonded to -CH2- and in equation (XII) -X- is R c1 -CH2- is bonded, The N-terminal modification group A is a blocking group Abl or an amino acid Aaa. compound. Embodiment 2. Formula (I)

[0053] [ka]

[0054] cyclic peptide and a compound comprising an N-terminal modification group A bonded to Xaa1, The aforementioned peptide sequence is drawn from left to right in the direction from the N-terminus to the C-terminus. Xaa1 is equation (II).

[0055] [ka]

[0056] It is a residue of the amino acid, R 1a is -NH-, R 1b is H or CH3, n=0 or 1, The aforementioned N-terminal modification group A is covalently bonded to the nitrogen atom of Xaa1, The carbonyl group of Xaa1 is covalently bonded to the nitrogen of Xaa2. The sulfur atom of Xaa1 is covalently bonded to Yc as a thioether. Xaa2 is equation (III), (IV), or (XX)

[0057] [ka]

[0058] It is a residue of the amino acid, R 2a , R 2b , R2c Each of these is independently selected from the group consisting of (C1-C2) alkyl and H, and the (C1-C2) alkyl may be substituted with a substituent selected from the group consisting of OH, NH2, halogen, and (C5-C7) cycloalkyl. p = 0, 1, or 2, v=1 or 2, w = 1, 2, or 3, The amino acid of formula (IV) may be substituted at positions 3 and 4 of the indicated ring with one or two substituents selected from the group consisting of methyl, OH, NH2, and F. Xaa3 is expression (V) or (XX)

[0059] [ka]

[0060] It is a residue of the amino acid, X 3 CH2, CF2, CH-R 3b Selected from the group consisting of S, O, and NH, p=1 or 2, v=1 or 2, w = 1, 2, or 3, R 3a is H, methyl, OH, NH2, or F, R 3b is methyl, OH, NH2, or F, Xaa4 is equation (VI).

[0061] [ka]

[0062] It is a residue of the amino acid, R 4a H, OH, COOH, CONH2, X 4 , and -NH-CO-X 4 Selected from the group consisting of X 4X is selected from the group consisting of (C1-C6) alkyl, (C5-C6) aryl, and (C5-C6) heteroaryl, 4 It may be substituted with one or two substituents selected from the group consisting of methyl, CONH2, halogen, NH2, and OH. q = 1, 2, or 3, and one or two hydrogens of the one, two, or three CH2- groups are optionally substituted individually with methyl, ethyl, (C5-C6)aryl, or (C5-C6)heteroaryl groups. R 4b is methyl or H, Xaa5 structure (VII)

[0063] [ka]

[0064] It is a residue of the amino acid, R 5 The group selected is from the OH and NH2 groups. r = 1, 2, or 3, Xaa6 is an amino acid selected from the group consisting of aromatic L-α-amino acids and heteroaromatic L-α-amino acids. Xaa7 is equation (IX).

[0065] [ka]

[0066] It is an aminothiol or amino acid residue, R 7a -CO-XXX, -COOH, -CONH2, -CH2-OH, -(CO)-NH-R 7b ,-(CO)-(NR 7c )-R 7b , or H, where XXX is an amino acid or peptide that forms an amide bond with the carbonyl carbon atom, R 7b and R 7cEach of them is independently a (C1-C4) alkyl, The aforementioned amino acids or peptides are optionally substituted with Z groups. t is 1 or 2, Yc is given by equation (X).

[0067] [ka]

[0068] The structure is such that the sulfur atom of Xaa1 and the sulfur atom of Xaa7 are linked under the formation of two thioether linkages, thereby forming equation (XXI)

[0069] [ka]

[0070] It forms a ring structure, The substitution pattern of the aromatic group in formula (X) is ortho, meta, or para. n=0 or 1, t=1 or 2, Y 1 is CH or N, Y 2 is N or CR c1 And, R c1 is H or CH2-R c2 And, R c2 is equation (XI), (XII), or (XXII)

[0071] [ka]

[0072] It has the following structure: R c3 and R c4 Each is independently selected from the group consisting of H and (C1-C4) alkyl groups, R c5 is an H or Z group, u = 1, 2, 3, 4, 5, or 6, x and y are independently 1, 2, or 3. X = O or S In equations (XI) and (XXII), one of the nitrogen atoms is R c1 It is bonded to -CH2- and in equation (XII) -X- is R c1 -CH2- is bonded, The N-terminal modification group A is a blocking group Abl or an amino acid Aaa, and the amino acid Aaa may be substituted with a Z group as needed, and each Z group contains a chelator and, optionally, a linker. compound. Embodiment 3. R c5 However, it is a Z group that includes a chelator and, optionally, a linker. R 7a -CO-XXX, -COOH, -CONH2, -CH2-OH, -(CO)-NH-R 7b ,-(CO)-(NR 7c )-R 7b , or H, R 7b and R 7c Each of these is independently a (C1-C4) alkyl group, XXX is an amino acid or peptide that forms an amide bond with the carbonyl carbon atom, and the amino acid or peptide is not substituted with a Z group including a chelator and optionally a linker. If the N-terminal modifying group A is amino acid Aaa, then the amino acid Aaa is not substituted with a Z group including a chelator and optionally a linker. Preferably, the compound according to Embodiment 2 comprises only a single Z group including a chelator and optionally a linker. Embodiment 4. R 7aThe compound according to any one of Embodiments 2 and 3, wherein, unlike -CO-XXX, XXX is an amino acid or peptide that forms an amide bond with the carbonyl carbon atom, and if the N-terminal modifying group A is the amino acid Aaa, then the amino acid Aaa is not substituted with a Z group including a chelator and optionally a linker. Embodiment 5. R 7a A is -CO-XXX, where XXX is an amino acid or peptide that forms an amide bond with the carbonyl carbon atom, and the amino acid or peptide is substituted with a Z group containing a chelator and optionally a linker. R c1 or R c5 H is, If the N-terminal modifying group A is amino acid Aaa, then the amino acid Aaa is not substituted with a Z group including a chelator and optionally a linker. Preferably, the compound according to Embodiment 2 comprises only a single Z group including a chelator and optionally a linker. Embodiment 6. The N-terminal modification group A is an amino acid Aaa substituted with a Z group containing a chelator and optionally a linker, R c1 or R c5 H is, R 7a -CO-XXX-COOH, -CONH2, -CH2-OH, -(CO)-NH-R 7b ,-(CO)-(NR 7c )-R 7b , or H, R 7b and R 7c Each of these is independently a (C1-C4) alkyl group, XXX is an amino acid or peptide that forms an amide bond with the carbonyl carbon atom, and the amino acid or peptide is not substituted with a Z group including a chelator and optionally a linker. Preferably, the compound according to Embodiment 2 comprises only a single Z group including a chelator and optionally a linker. Embodiment 7. R 7aThe compound according to embodiment 6, wherein, unlike -CO-XXX, XXX is an amino acid or peptide that forms an amide bond with the carbonyl carbon atom. Embodiment 8. Each amino acid Aaa has the structure (XIV)

[0073]

Chemical formula

[0074] which is a D - amino acid residue or L - amino acid residue of R a2 is selected from the group consisting of (C1 - C6) alkyl, modified (C1 - C6) alkyl, (C1 - C3) alkyl, modified (C1 - C3), (C3 - C8) carbocycle, aryl, heteroaryl, and (C3 - C8) heterocycle, in the modified (C1 - C6) alkyl, one - CH2 - group is replaced by -S- or -O-, and in the modified (C1 - C3) alkyl, one of H is substituted by OH, F, or COOH, or two of H are substituted by F, and R a3 is a Z group, the compound according to any one of embodiments 2, 6, and 7. Embodiment 9. The blocking group Abl is R a1 -C(O)-, R a1 -S(O2)-, R a1 -NH - C(O)-, and R a1 -O - C(O)-, and R a1 is independently selected from the group consisting of OH, F, COOH, (C3 - C8) cycloalkyl, aryl, heteroaryl, and (C3 - C8) heterocycle as needed, is (C1 - C8) alkyl substituted by up to two substituents, and in (C1 - C8) alkyl, one of the -CH2 - groups is replaced by -S- or -O- as needed, the compound according to any one of embodiments 1, 2, 3, 4, and 5. Embodiment 10. The blocking group Abl is R a1 -C(O)- or Ra1 -S(O2)-, and R a1 is (C1-C6) alkyl, and optionally one of the -CH2- groups is replaced by -S- or -O-, the compound according to embodiment 9. Embodiment 11. The blocking group Abl is hexanoyl or pentylsulfonyl, preferably the blocking group Abl is hexanoyl, the compound according to embodiment 10. Embodiment 12. The amino acid Aaa is respectively of structure (XIV)

[0075]

Chemical formula

[0076] is a D-amino acid residue or an L-amino acid residue of R a2 is selected from the group consisting of (C1-C6) alkyl, modified (C1-C6) alkyl, (C1-C3) alkyl, modified (C1-C3) alkyl, (C3-C8) carbocycle, aryl, heteroaryl, and (C3-C8) heterocycle, and in the modified (C1-C6) alkyl one of the -CH2- groups is replaced by -S- or -O-, and in the modified (C1-C3) alkyl one of the Hs is substituted by OH, F, or COOH, or two of the Hs are substituted by F, and R a3 is preferably H or acetyl, the compound according to any one of embodiments 1, 2, 3, 4, 5. Embodiment 13. R a2 is (C1-C6) alkyl, and one of the -CH2- groups of the (C1-C6) is replaced by -S-, the compound according to embodiment 12. Embodiment 14. Aaa is selected from the group consisting of amino acid residues of Nle, nle, Met, and met, and their derivatives, the compound according to any one of embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13, preferably any one of 12 to 13. Embodiment 15. The compound according to any one of Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 14, wherein Xaa1 is a D-amino acid residue selected from the group consisting of cys, hcy, and pen, or Xaa1 is an L-amino acid residue selected from the group consisting of Cys, Hcy, and Pen. Embodiment 16. The compound according to Embodiment 15, wherein Xaa1 is Cys. Embodiment 17. The compound according to any one of Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 16, wherein Xaa2 is an amino acid residue selected from the group consisting of Pro, Gly, Nmg, and their derivatives. Embodiment 18. The compound according to any one of Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, and 17, wherein Xaa3 is an amino acid residue selected from the group consisting of Pro, Hyp, Tfp, Cfp, Dmp, Aze, and Pip, and their derivatives. Embodiment 19. The compound according to any one of Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18, wherein Xaa4 is an amino acid residue selected from the group consisting of Thr, Hse, Asn, Gln, and Ser, and their derivatives. Embodiment 20. Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, wherein Xaa5 is an amino acid residue selected from the group consisting of Gln and Glu, and their derivatives. , the compounds described in any one of the following items: 11, 12, 13, 14, 15, 16, 17, 18, and 19. Embodiment 21. Xaa6 is formula (VIIIa), (VIIIb), (VIIIc), and (VIIId)

[0077] [ka]

[0078] It is any one of the amino acid residues, R 6a and R 6b Each of these is independently selected from the group consisting of H, methyl, ethyl, propyl, and isopropyl. R 6c The ∫ represents 0 to 3 substituents, and each substituent independently represents Cl, F, Br, NO2, NH2, CN, CF3, OH, OR 6d , and selected from the group consisting of C1-C4 alkyl groups, R 6d is selected from the group consisting of methyl, ethyl, propyl, and isopropyl, A compound according to any one of Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20, wherein s is 0 or 1. Embodiment 22. Xaa6 is formula (VIIIa), (VIIIb), (VIIIc), and (VIIId)

[0079] [ka]

[0080] It is any one of the amino acid residues, R 6a and R 6b These are H, R 6c The ∫ represents 0 to 2 substituents, and each substituent independently represents Cl, F, Br, NO2, NH2, CN, CF3, OH, OR 6d Selected from the group consisting of , and methyl, R 6d is selected from the group consisting of methyl, ethyl, propyl, and isopropyl, The compound according to Embodiment 21, wherein s is 0. Embodiment 23. The compound according to any one of Embodiments 21 to 22, wherein Xaa6 is an amino acid residue selected from the group consisting of Phe, Ocf, Ppa, Thi, 1Ni, Otf, and Mpa, and their derivatives. Embodiment 24. Embodiments 1, 2, 3, 4, and 5, wherein Xaa7 is an aminothiol residue selected from the group consisting of Cys, Cysol, AET, Hcy, cys, and hcy. A compound described in any one of the following items: 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 23. Embodiment 25. The compound according to Embodiment 24, wherein Xaa7 is an aminothiol residue selected from the group consisting of Cys, Cysol, and AET. Embodiment 26. Formula (LI), (LII), (LIII), or (LIV)

[0081] [ka]

[0082] A compound according to 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, and 25. Embodiment 27. Formula (LI), (LII), (LIII), or (LIV)

[0083] [ka]

[0084] A compound comprising the structure 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, and 25, preferably the compound according to any one of claims 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, and 25. Embodiment 28. R c2 Equations (XXIIa), (XIb), and (XIIa)

[0085] [ka]

[0086] It is one of the following structures: R c4 is H or methyl, u = 1, 2, 3, 4, or 5, In formulas (XIb) and (XXIIa), one of the nitrogen atoms is R c1 It is bonded to -CH2- and in equation (XIIa), -S- is R c1 A compound according to 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, and 27, which is bonded to -CH2-. Embodiment 29. Yc is given by equation (XIII)

[0087] [ka]

[0088] The compound according to 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, and 28, having the structure of the compound described above. Embodiment 30. Yc comprises an NH group, preferably a reactive NH group, wherein the NH group enables conjugation to the Yc portion, and preferably the NH group is structural R c2 Provided by R c2 The formulas (XXIb), (XIc), and (XIIb)

[0089] [ka]

[0090] A group consisting of any one of the following structures is selected, R c4 is H or methyl, A compound according to 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, and 29, wherein u = 1, 2, 3, 4, or 5. Embodiment 31. The structure R c2 is formula (XXIIb) or (XIIc)

[0091] [ka]

[0092] The compounds described in 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, and 30. Embodiment 32. A compound according to any one of Embodiments 30 to 31, A compound comprising a Z group, wherein the Z group is covalently bonded to Yc, preferably a structure of formula (X), and the Z group comprises a chelator and optionally a linker. Embodiment 33. The Z group is R c2 Covalently bonded to equations (XXIIc), (XId), and (XIId)

[0093] [ka]

[0094] It forms one of the following structures, R c4 is H or methyl, The compound according to Embodiment 32, wherein u = 1, 2, 3, 4, or 5. Embodiment 34. The Z group includes a linker, and the linker converts the chelator to Yc, preferably R c2 A compound according to any one of embodiments 32 to 33, which is covalently linked to the other. Embodiment 35. Between Yc and the linker, preferably Rc2 The compound according to embodiment 34, wherein the covalent linkage between the linker and the compound is an amide. Embodiment 36. The compound according to any one of Embodiments 34 to 35, wherein the chelator is covalently linked to the linker, and the covalent linkage is selected from the group comprising amide linkage, urea linkage, carbamate linkage, ester linkage, ether linkage, thioether linkage, sulfonamide, triazole, and disulfide linkage. Embodiment 37. The compound according to any one of Embodiments 32, 33, 34, 35, and 36, preferably any one of claims 34, 35, and 36, wherein the linker is selected from the group comprising Ttds, O2Oc, Apac, Gly, Bal, Gab, Mamb, Pamb, Ppac, 4Amc, Inp, Sni, Rni, Nmg, Cmp, PEG6, PEG12, and other PEG-amino acids, most preferably Ttds, O2Oc, Apac, 4Amc, PEG6, and PEG12. Embodiment 38. The chelator is covalently connected to Yc, preferably R c2 A compound according to any one of embodiments 32 to 33, which is covalently linked to the other. Embodiment 39. The compound according to Embodiment 38, wherein the chelator is directly connected to Yc. Embodiment 40. The compound according to any one of Embodiments 38 to 39, wherein the Z group lacks any linker. Embodiment 41. Between Yc and the chelator, preferably R c2 The compound according to any one of embodiments 38, 39, and 40, wherein the covalent linkage between the compound and the chelator is an amide. Embodiment 42. The chelator is DOTA, DOTAGA, NOTA, NODAGA, NODA-MPAA, HBED, TETA, CB-TE2A, DTPA, DFO, Macropa, HOPO, TRAP, THP, DATA, NOTP, sarcophagine, FSC, NETA, H4octapa, Pycup, N x S 4-x(N4, N2S2, N3S), Hynic, 99m Compounds selected from the group consisting of Tc(CO)3-chelators, more preferably DOTA, DOTAGA, NOTA, NODAGA, NODA-MPAA, HBED, CB-TE2A, DFO, THP, N4, and most preferably DOTA, DOTAGA, NOTA, and NODAGA, according to 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, 33, 34, 35, 36, 37, 38, 39, 40, and 41, preferably according to any one of Embodiments 32, 33, 34, 35, 36, 37, 38, 39, 40, and 41. Embodiment 43. 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 A compound according to any one of claims 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, and 42, preferably any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 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, wherein the N-terminal modifying group A is an amino acid Aaa, the compound comprises a Z group covalently bonded to the amino acid Aaa, and the Z group comprises a chelator and optionally a linker. Embodiment 44. The compound according to Embodiment 43, wherein the Z group includes a linker, and the linker covalently links the chelator to the amino acid Aaa, preferably to the α-nitrogen of the amino acid Aaa. Embodiment 45. The compound according to Embodiment 44, wherein the covalent linkage between the linker and the α-nitrogen of the amino acid Aaa is an amide. Embodiment 46. The compound according to any one of Embodiments 44 to 45, wherein the chelator is covalently linked to the linker, and the covalent linkage is selected from the group comprising amide linkage, urea linkage, carbamate linkage, ester linkage, ether linkage, thioether linkage, sulfonamide, triazole, and disulfide linkage. Embodiment 47. The compound according to any one of Embodiments 43, 44, 45, and 46, wherein the linker is selected from the group comprising Ttds, O2Oc, Apac, Gly, Bal, Gab, Mamb, Pamb, Ppac, 4Amc, Inp, Sni, Rni, Nmg, Cmp, PEG6, PEG12, and other PEG-amino acids, most preferably Ttds, O2Oc, Apac, 4Amc, PEG6, and PEG12, and preferably the linker amino acid is selected from the group comprising Tdts, O2Oc, and PEG6. Embodiment 48. The compound according to any one of Embodiments 43, 44, 45, 46, and 47, wherein the chelator is covalently linked to the amino acid Aaa. Embodiment 49. The compound according to Embodiment 48, wherein the chelator is directly linked to the amino acid Aaa. Embodiment 50. The compound according to any one of Embodiments 48 to 49, wherein the Z group lacks any linker. Embodiment 51. The compound according to any one of Embodiments 48, 49, and 50, wherein the covalent linkage between the amino acid Aaa and the chelator is an amide. Embodiment 52. The chelator is DOTA, DOTAGA, NOTA, NODAGA, NODA-MPAA, HBED, TETA, CB-TE2A, DTPA, DFO, Macropa, HOPO, TRAP, THP, DATA, NOTP, sarcophagine, FSC, NETA, H4octapa, Pycup, N x S 4-x (N4, N2S2, N3S), Hynic, 99mCompounds according to any one of embodiments 43, 44, 45, 46, 47, 48, 49, 50, and 51, selected from the group consisting of Tc(CO)3-chelators, more preferably DOTA, DOTAGA, NOTA, NODAGA, NODA-MPAA, HBED, CB-TE2A, DFO, THP, N4, and most preferably DOTA, DOTAGA, NOTA, and NODAGA. Embodiment 53. An amino acid or peptide is bound to Xaa7, and the majority of the amino acids in this peptide are charged or polar, and the net charge of the peptide is -2, -1, 0, +1, or +2, in 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. A compound according to any one of claims 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, and 52, preferably the 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, and 42. Embodiment 54. The peptide is of formula (XXXa~f) Xaa10-Xaa11-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16 (XXXa) Xaa10-Xaa11-Xaa12-Xaa13-Xaa14-Xaa15 (XXXb) Xaa10-Xaa11-Xaa12-Xaa13-Xaa14 (XXXc) Xaa10-Xaa11-Xaa12-Xaa13 (XXXd) Xaa10-Xaa11-Xaa12 (XXXe) Xaa10-Xaa11 (XXXf) Selected from the group consisting of peptides, Xaa10 is Asp, asp, Bal, Gly, Gab, Ser, Nmg, Bhf, Lys, Ttds, or Bhk. Xaa11 is His, his, Lys, Ttds, Arg, Ape, or Ala, Xaa12 is Phe, Nmf, Tic, Aic, Ppa, Mpa, Amf, Nmf, phe, Lys, Ape, Ttds, and Ppa. Xaa13 is Arg, Lys, Ape, Ttds, or arg. Xaa14 is Asp, Ala, asp, Lys, Ape, or Ttds. Xaa15 is Ttds, Ape, or Lys. Xaa16 is either Lys or Ape. as needed, Xaa11 and Xaa12 combine to form a single amino acid selected from the group consisting of Gab, Pamb, Cmp, Pamb, and Mamb, as needed. Xaa10, Xaa11, and Xaa12 combine to form a single amino acid selected from the group consisting of Gab, Pamb, Cmp, Pamb, and Mamb. The compound according to Embodiment 53, wherein in the peptide of formula (XXXa~f), Ape is a C-terminal construction block if present. Embodiment 55. The compound according to any one of Embodiments 53 to 54, wherein the amino acid bound to Xaa7 is Xaa10 of claim 46, and preferably the amino acid bound to Xaa7 is Asp, asp, Bal, Gly, Gab, Ser, Nmg, Bhf, Lys, Ape, Ttds, or Bhk. Embodiment 56. The compound according to any one of Embodiments 53 to 55, wherein the Z group is covalently bonded to the peptide, preferably to the C-terminal amino acid of the peptide, and the Z group comprises a chelator and optionally a linker. Embodiment 57. The compound according to Embodiment 56, wherein the Z group is covalently bonded to the C-terminal amino acid of the peptide, preferably to one of the C-terminal amino acids of the peptides of formula (XXXa), (XXXb), (XXXc), (XXXd), (XXXe), and (XXXf). Embodiment 58. The compound according to any one of Embodiments 53, 54, and 55, wherein the Z group is covalently bonded to an amino acid bonded to Xaa7, and the Z group comprises a chelator and, optionally, a linker. Embodiment 59. The compound according to any one of Embodiments 53, 54, 55, 56, 57, and 58, wherein the Z group includes a linker, and the linker preferably covalently links the chelator to an amino acid bound to Xaa7 when the peptide is not bound to Xaa7, or the linker covalently links the chelator to the C-terminus of the peptide, preferably to one C-terminal amino acid of any one of the peptides of formula (LI), (LII), (LIII), and (LIV). Embodiment 60. The compound according to Embodiment 59, wherein the covalent linkage is an amide bond. Embodiment 61. The chelator is covalently connected to the linker, and the covalent A compound according to any one of embodiments 59 to 60, wherein the binding linkage is selected from the group comprising amide linkage, urea linkage, carbamate linkage, ester linkage, ether linkage, thioether linkage, sulfonamide, triazole, and disulfide linkage. Embodiment 62. The compound according to any one of Embodiments 59, 60, and 61, wherein the linker is selected from the group consisting of Ttds, O2Oc, Apac, Gly, Bal, Gab, Mamb, Pamb, Ppac, 4Amc, Inp, Sni, Rni, Nmg, Cmp, PEG6, PEG12, and other PEG-amino acids. Embodiment 63. The compound according to Embodiment 62, wherein the linker is selected from the group consisting of Ttds, O2Oc, Apac, 4Amc, PEG6, and PEG12. Embodiment 64. The compound according to any one of Embodiments 56, 57, and 58, wherein the chelator is covalently linked to an amino acid bound to Xaa7, or the chelator is covalently linked to the C-terminal amino acid of the peptide, preferably one C-terminal amino acid of the peptides of formula (LI), (LII), (LIII), and (LIV). Embodiment 65. The compound according to Embodiment 64, wherein the chelator is directly linked to the amino acid bound to Xaa7, or to the C-terminal amino acid of the peptide, preferably to one of the C-terminal amino acids of the peptides of formula (LI), (LII), (LIII), and (LIV). Embodiment 66. The compound according to any one of Embodiments 64 to 65, wherein the Z group lacks any linker. Embodiment 67. The compound according to any one of Embodiments 64, 65, and 66, wherein the covalent linkage between the chelator and the amino acid bound to Xaa7 and the covalent linkage between the chelator and the C-terminal amino acid of the peptide, preferably one C-terminal amino acid from the peptides of formula (LI), (LII), (LIII), and (LIV), is an amide bond. Embodiment 68. The chelator is DOTA, DOTAGA, NOTA, NODAGA, NODA-MPAA, HBED, TETA, CB-TE2A, DTPA, DFO, Macropa, HOPO, TRAP, THP, DATA, NOTP, sarcophagine, FSC, NETA, H4octapa, Pycup, N x S 4-x (N4, N2S2, N3S), Hynic, 99m Compounds according to any one of embodiments 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, and 67, more preferably selected from the group consisting of Tc(CO)3-chelators, DOTA, DOTAGA, NOTA, NODAGA, NODA-MPAA, HBED, CB-TE2A, DFO, THP, N4, and most preferably DOTA, DOTAGA, NOTA, and NODAGA. Embodiment 69. The following formula

[0095] [ka]

[0096] The diastereomer and the following formula

[0097] [ka]

[0098] A compound according to 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, 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, and 68, wherein the stereochemically unspecified stereocenters (marked with asterisks) are individually and independently R-type or S-type. Embodiment 70. The following formula

[0099] [ka]

[0100] compounds H-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-Ttds-Lys(Bio)-NH2 (3BP-2881) The following formula

[0101] [ka]

[0102] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-2974), has the following formula:

[0103] [ka]

[0104] The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-2975), The following formula

[0105] [ka]

[0106] The compound H-met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-2976), The following formula

[0107] [ka]

[0108] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-Ttds-Lys(DOTA)-NH2 (3BP-3105), The following formula

[0109] [ka]

[0110] The compound DOTA-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-3168), The following formula

[0111] [ka]

[0112] The compound DOTA-Ttds-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-3169), The following formula

[0113] [ka]

[0114] The compound DOTA-Ttds-Leu-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-3172), The following formula

[0115] [ka]

[0116] The compound Ac-Met-[cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-3175), The following formula

[0117] [ka]

[0118] The compound Ac-met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-3187), The following formula

[0119] [ka]

[0120] The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Nmf-Arg-Asp-NH2 (3BP-3188), The following formula

[0121] [ka]

[0122] The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Tic-Arg-Asp-NH2 (3BP-3189), The following formula

[0123] [ka]

[0124] The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Aic-Arg-Asp-NH2 (3BP-3190), The following formula

[0125] [ka]

[0126] The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Ppa-Arg-Asp-NH2 (3BP-3191), The following formula

[0127] [ka]

[0128] The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Mpa-Arg-Asp-NH2 (3BP-3192), The following formula

[0129] [ka]

[0130] The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Thi-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-3193), The following formula

[0131] [ka]

[0132] The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-Ala-Phe-Arg-Asp-NH2 (3BP-3195), The following formula

[0133] [ka]

[0134] The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Ala-Arg-Asp-NH2 (3BP-3196), The following formula

[0135] [ka]

[0136] The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Ala-NH2 (3BP-3198), The following formula

[0137] [ka]

[0138] The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-NH2 (3BP-3200), The following formula

[0139] [ka]

[0140] The compound Ac-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-3202), The following formula

[0141] [ka]

[0142] The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-P he-Cys]-Asp-His-Amf-Arg-Asp-NH2 (3BP-3203), The following formula

[0143] [ka]

[0144] The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-his-Phe-Arg-Asp-NH2 (3BP-3210), The following formula

[0145] [ka]

[0146] The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-phe-Arg-Asp-NH2 (3BP-3211), The following formula

[0147] [ka]

[0148] The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-arg-Asp-NH2 (3BP-3212), The following formula

[0149] [ka]

[0150] The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-asp-NH2 (3BP-3213), The following formula

[0151] [ka]

[0152] The compound Ac-Met-[Cys(3MeBn)-Gly-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-3214), The following formula

[0153] [ka]

[0154] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Nmf-Arg-Ttds-Lys(DOTA)-NH2 (3BP-3275), The following formula

[0155] [ka]

[0156] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-phe-Arg-Ttds-Lys(DOTA)-NH2 (3BP-3276), The following formula

[0157] [ka]

[0158] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Ppa-arg-Ttds-Lys(DOTA)-NH2 (3BP-3277), The following formula

[0159] [ka]

[0160] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-NH2 (3BP-3288), The following formula

[0161] [ka]

[0162] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-Arg-NH2 (3BP-3299), The following formula

[0163] [ka]

[0164] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-Gab-Arg-NH2 (3BP-3300), The following formula

[0165] [ka]

[0166] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-Pamb-Arg-NH2 (3BP-3301), The following formula

[0167] [ka]

[0168] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-Cmp-Arg-NH2 (3BP-3302) The following formula

[0169] [ka]

[0170] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Pamb-Arg-NH2 (3BP-3303), The following formula

[0171] [ka]

[0172] The compound DOTA-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-NH2 (3BP-3319), The following formula

[0173] [ka]

[0174] The compound DOTA-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-NH2 (3BP-3320), The following formula

[0175] [ka]

[0176] The compound DOTA-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-Pamb-Arg-NH2 (3BP-3321), The following formula

[0177] [ka]

[0178] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-Mamb-Arg-NH2 (3BP-3324), The following formula

[0179] [ka]

[0180] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-NH2 (3BP-3349), The following formula

[0181] [ka]

[0182] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Bal-OH (3BP-3371), The following formula

[0183] [ka]

[0184] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-Ttds-Lys(DOTA)-NH2 (3BP-3395), The following formula

[0185] [ka]

[0186] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-Ttds-Lys(DOTA)-NH2 (3BP-3396), The following formula

[0187] [ka]

[0188] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Bhk(DOTA)-OH (3BP-3397), The following formula

[0189] [ka]

[0190] The compound DOTA-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Bal-OH (3BP-3398), The following formula

[0191] [ka]

[0192] The compound DOTA-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3401), The following formula

[0193] [ka]

[0194] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-Ape(DOTA) (3BP-3403), The following formula

[0195] [ka]

[0196] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-Ttds-Ape(DOTA) (3BP-3404), The following formula

[0197] [ka]

[0198] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Otf-Cys]-NH2 (3BP-3409), The following formula

[0199] [ka]

[0200] The compound pentyl NH-urea-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3425), The following formula

[0201] [ka]

[0202] The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3426), The following formula

[0203] [ka]

[0204] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3476), The following formula

[0205] [ka]

[0206] The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Bhk(DOTA-Ttds)-OH (3BP-3489), The following formula

[0207] [ka]

[0208] The compound pentyl-SO2-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3514), The following formula

[0209] [ka]

[0210] The compound Hex-[Cys(2Lut)-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3518), The following formula

[0211] [ka]

[0212] The compound Hex-[Cys(3Lut)-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3519), The following formula

[0213] [ka]

[0214] The compound Hex-[Cys(tMeBn(DOTA-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3555), The following formula

[0215] [ka]

[0216] The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-1Ni-Cys]-OH (3BP-3650), The following formula

[0217] [ka]

[0218] The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Bal-OH (3BP-3651), The following formula

[0219] [ka]

[0220] The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-NH2 (3BP-3652), The following formula

[0221] [ka]

[0222] The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Glu-Phe-Cys]-NH2 (3BP-3653), The following formula

[0223] [ka]

[0224] The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-AET] (3BP-3654), The following formula

[0225] [ka]

[0226] The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Gly-OH (3BP-3656), The following formula

[0227] [ka]

[0228] The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Gab-OH (3BP-3657), The following formula

[0229] [ka]

[0230] The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Ser-OH (3BP-3658), The following formula

[0231] [ka]

[0232] The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Nmg-OH (3BP-3659), The following formula

[0233] [ka]

[0234] The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Bhf-OH (3BP-3660), The following formula

[0235] [ka]

[0236] The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Mpa-Cys]-OH (3BP-3664), The following formula

[0237] [ka]

[0238] The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-OH (3BP-3665), The following formula

[0239] [ka]

[0240] The compound Hex-[Cys(tMeBn(DOTA-AET))-Nmg-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3678), The following formula

[0241] [ka]

[0242] The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Hyp-Th r-Gln-Phe-Cys]-OH (3BP-3679), The following formula

[0243] [ka]

[0244] The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Otf-Cys]-OH (3BP-3680), The following formula

[0245] [ka]

[0246] The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-asp-NH2 (3BP-3681), The following formula

[0247] [ka]

[0248] The compound pentyl-SO2-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3690), The following formula

[0249] [ka]

[0250] The compound pentyl-SO2-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-3691), The following formula

[0251] [ka]

[0252] The compound pentyl-SO2-[Cys(tMeBn(DOTA-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3692), The following formula

[0253] [ka]

[0254] The compound Hex-[Cys(tMeBn(InDOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-NH2 (3BP-3712), The following formula

[0255] [ka]

[0256] The compound Hex-[Cys(tMeBn(InDOTA-AET))-Pro-Pro-Thr-Gln-Phe-AET] (3BP-3713), The following formula

[0257] [ka]

[0258] The compound Hex-[Cys(tMeBn(InDOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Gly-OH (3BP-3714), The following formula

[0259] [ka]

[0260] The compound Hex-[Cys(tMeBn(InDOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Nmg-OH (3BP-3715), The following formula

[0261] [ka]

[0262] The compound Hex-[Cys(tMeBn(InDOTA-AET))-Nmg-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3716), The following formula

[0263] [ka]

[0264] The compound pentyl-SO2-[Cys(tMeBn(InDOTA-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3717), The following formula

[0265] [ka]

[0266] The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Bal-NH2 (3BP-3736), The following formula

[0267] [ka]

[0268] The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Nmg-NH2 (3BP-3737), The following formula

[0269] [ka]

[0270] The compound Hex-[Cys(tMeBn(DOTA-AET))-Nmg-Pro-Thr-Gln-Phe-Cys]-NH2 (3BP-3744), The following formula

[0271] [ka]

[0272] The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cysol] (3BP-3767), The following formula

[0273] [ka]

[0274] The compound Hex-[Cys(tMeBn(InDOTA-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3770), The following formula

[0275] [ka]

[0276] The compound Hex-[Cys(tMeBn(DOTA-PP))-Nmg-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3771), The following formula

[0277] [ka]

[0278] The compound Hex-[Cys-(tMeBn(H-O2Oc-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3967), The following formula

[0279] [ka]

[0280] The compound H-Ahx-Ttds-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3980), The following formula

[0281] [ka]

[0282] The compound Hex-[Cys-(tMeBn(H-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3981), The following formula

[0283] [ka]

[0284] The compound Hex-[Cys-(tMeBn(H-O2Oc-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-4003), The following formula

[0285] [ka]

[0286] The compound H-Ahx-Ttds-Nle-[Cys-(tMeBn(DOTA-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-4004), The following formula

[0287] [ka]

[0288] The compound Hex-[Cys-(tMeBn(N4Ac-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4063), The following formula

[0289] [ka]

[0290] The compound Hex-[Cys-(tMeBn(N4Ac-O2Oc-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4088), The following formula

[0291] [ka]

[0292] The compound Hex-[Cys-(tMeBn(H-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4089), The following formula

[0293] [ka]

[0294] The compound Hex-[D-Cys-(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4109), The following formula

[0295] [ka]

[0296] The compound N4Ac-Ttds-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4161), The following formula

[0297] [ka]

[0298] The compound Hex-[Cys-(tMeBn(NODAGA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4162), The following formula

[0299] [ka]

[0300] The compound Hex-[Cys-(tMeBn(N4Ac-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4168), The following formula

[0301] [ka]

[0302] The compound Hex-[Cys-(tMeBn(N4Ac-O2Oc-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4169), The following formula

[0303] [ka]

[0304] The compound Hex-[Cys-(tMeBn(Bio-Ttds-Ttds-Ttds-Ttds-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4170), The following formula

[0305] [ka]

[0306] The compound Hex-[Cys-(tMeBn(H-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4181), The following formula

[0307] [ka]

[0308] The compound Hex-[Cys(tMeBn(ATTO488-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4182), The following formula

[0309] [ka]

[0310] The compound Hex-[Cys-(tMeBn(GaNODAGA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4184), The following formula

[0311] [ka]

[0312] The compound Hex-[Cys-(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4186), The following formula

[0313] [ka]

[0314] The compound Hex-[Cys-(tMeBn(DTPA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4214), The following formula

[0315] [ka]

[0316] The compound N4Ac-Ttds-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4219), The following formula

[0317] [ka]

[0318] The compound N4Ac-PEG6-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4221), The following formula

[0319] [ka]

[0320] The compound N4Ac-Glu-Ttds-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4222), The following formula

[0321] [ka]

[0322] The compound Hex-[Cys-(tMeBn(DTPA-O2Oc-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4224), The following formula

[0323] [ka]

[0324] The compound N4Ac-Efa-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4243), The following formula

[0325] [ka]

[0326] The compound N4Ac-gGlu-Ttds-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4245), The following formula

[0327] [ka]

[0328] The compound N4Ac-Glu(AGLU)-Ttds-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4246), has the following formula:

[0329] [ka]

[0330] The compound N4Ac-gGlu-Ttds-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4247), The following formula

[0331] [ka]

[0332] The compound N4Ac-Glu(AGLU)-Ttds-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4249), has the following formula:

[0333] [ka]

[0334] The compound Hex-[Cys-(tMeBn(DOTA-AET))-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4250), The following formula

[0335] [ka]

[0336] The compound Hex-[Cys-(tMeBn(NODAGA-O2Oc-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4251), The following formula

[0337] [ka]

[0338] The compound N4Ac-Glu(AGLU)-Glu(AGLU)-Ttds-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4266), The following formula

[0339] [ka]

[0340] The compound Hex-[Cys-(tMeBn(N4Ac-Ttds-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4299), The following formula

[0341] [ka]

[0342] The compound Hex-[Cys-(tMeBn(N4Ac-PEG6-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4300), The following formula

[0343] [ka]

[0344] The compound Hex-[Cys-(tMeBn(H-SAc-Ser-Ser-Ser-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4301), The following formula

[0345] [ka]

[0346] The compound Hex-[Cys-(tMeBn(H-Asp-Asp-Cys-Ttds-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-43 02), The following formula

[0347] [ka]

[0348] The compound Hex-[Cys-(tMeBn(H-Asp-Asp-Cys-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4303), The following formula

[0349] [ka]

[0350] The compound Hex-[Cys-(tMeBn(H-SAc-Ser-Ser-Ser-Ttds-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4308), The following formula

[0351] [ka]

[0352] The compound Hex-[Cys-(tMeBn(DTPA2-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4309), The following formula

[0353] [ka]

[0354] The compound Hex-[Cys-(tMeBn(NOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4310), The following formula

[0355] [ka]

[0356] The compound Hex-[Cys-(tMeBn(H-HYNIC-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4342), The following formula

[0357] [ka]

[0358] The compound Hex-[Cys-(tMeBn(NOTA-Ttds-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4344), The following formula

[0359] [ka]

[0360] The compound Hex-[Cys-(tMeBn(DTPA2-Ttds-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4352), The following formula

[0361] [ka]

[0362] The compound Hex-[Cys-(tMeBn(DTPA2-PEG6-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4353), The following formula

[0363] [ka]

[0364] The compound Hex-[Cys-(tMeBn(DTPABzl-Glutar-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4366), has the following formula:

[0365] [ka]

[0366] The compound Hex-[Cys(tMeBn(LuDOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-Gab-Arg-Ttds-Lys(AF488)-NH2 (3BP-4372), The following formula

[0367] [ka]

[0368] The compound Hex-[Cys(tMeBn(LuDOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-Gab-Arg-Ttds-Ttds-Ttds-Lys(AF488)-NH2 (3BP-4373), The following formula

[0369] [ka]

[0370] The compound Hex-[Cys-(tMeBn(H-HYNIC-Ttds--AET))- Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4376), The following formula

[0371] [ka]

[0372] The compound Hex-[Cys-(tMeBn(PCTA--AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4379), The following formula

[0373] [ka]

[0374] The compound Hex-[Cys-(tMeBn(NOPO--AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4380), The following formula

[0375] [ka]

[0376] The compound Hex-[Cys-(tMeBn(HBED--AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4381), The following formula

[0377] [ka]

[0378] The compound Hex-[Cys-(tMeBn(DATA--AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4382), The following formula

[0379] [ka]

[0380] The compound DOTA-Ttds-Nle-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4386), The following formula

[0381] [ka]

[0382] The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-Ttds-Lys(DOTA)-NH2 (3BP-4391), The following formula

[0383] [ka]

[0384] The compound DOTA-Ttds-Nle-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-Ttds-Lys(DOTA)-NH2 (3BP-4392), and The following formula

[0385] [ka]

[0386] The compound DOTA-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Th r-Gln-Phe-Cys]-Asp-Ttds-Lys(DOTA)-NH2 (3BP-4393) A compound according to 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, 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, and 69, selected from the group consisting of the above. Embodiment 71. The following formula

[0387] [ka]

[0388] The compounds Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3554) and The following formula

[0389] [ka]

[0390] The compound Hex-[Cys(tMeBn(DOTA-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 A compound according to 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, 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, and 70, which is different from a compound selected from the group consisting of (3BP-3407). Embodiment 72. Any S atom that can be oxidized, preferably a S atom of a thioether group. The compound according to 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, 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, and 71, wherein the child exists as -S-, -S(O)-, or -S(O2)-, or a mixture thereof. Embodiment 73. A compound according to 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, 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, and 72, which can bind to fibroblast-activating protein (FAP). Embodiment 74. A compound according to 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, 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, and 73, comprising a diagnostically active or therapeutically active nuclide. Embodiment 75. The following formula

[0391] [ka]

[0392] The compound Hex-[Cys(tMeBn(InDOTA-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3590), The following formula

[0393] [ka]

[0394] The compound Hex-[Cys(tMeBn(LuDOTA-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3591), The following formula

[0395] [ka]

[0396] The compound Hex-[Cys(tMeBn(GaDOTA-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3592), The following formula

[0397] [ka]

[0398] The compound Hex-[Cys(tMeBn(EuDOTA-PP))-Pro-Pro-T hr-Gln-Phe-Cys]-Asp-NH2 (3BP-3661), The following formula

[0399] [ka]

[0400] The compound Hex-[Cys(tMeBn(InDOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3623), The following formula

[0401] [ka]

[0402] The compound Hex-[Cys(tMeBn(LuDOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3624), The following formula

[0403] [ka]

[0404] The compound Hex-[Cys(tMeBn(EuDOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3662), and The following formula

[0405] [ka]

[0406] The compound Hex-[Cys(tMeBn(GaDOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3949), The following formula

[0407] [ka]

[0408] The compound Hex-[Cys-(tMeBn(CuDOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4293), The following formula

[0409] [ka]

[0410] The compound Hex-[Cys-(tMeBn(ZnDOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4343) A compound according to Embodiment 74, which is different from a compound selected from the group consisting of the above. Embodiment 76. The compound according to any one of Embodiments 74 and 75, wherein the diagnostically active nuclide is a diagnostically active radionuclide. Embodiment 77. The diagnostically active radionuclide is 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, 201 Tl, 203 Pb, 18 F, 76 Br, 77 Br, 123 I, 124 I, 125 I, preferably 43 Sc, 44 Sc, 64 Cu, 67 Ga, 68 Ga, 86 Y, 89 Zr, 99m Tc, 111 In, 152 Tb, 155 Tb, 203 Pb, 18 F, 76 Br, 77 Br, 123 I, 124 I, 125 I, most preferably 64 Cu, 68 Ga, 89 Zr, 99m Tc, 111 In, 18 F,123 I, and 124 A compound according to embodiment 76, selected from the group consisting of I. Embodiment 78. The compound according to Embodiment 76, wherein the therapeutically active nuclide is a therapeutically active radionuclide. Embodiment 79. The therapeutically active radionuclide is 47 Sc, 67 Cu, 89 Sr, 90 Y, 153 Sm, 149 Tb, 161 Tb, 177 Lu, 186 Re, 188 Re, 212 Pb, 213 Bi, 223 Ra, 225 Ac, 226 Th, 227 Th, 131 I, 211 At, preferably 47 Sc, 67 Cu, 90 Y, 177 Lu, 188 Re, 212 Pb, 213 Bi, 225 Ac, 227 Th, 131 I, 211 At, most preferably 90 Y, 177 Lu, 225 Ac, 227 Th, 131 I, and 211 A compound according to embodiment 78, selected from the group consisting of At. Embodiment 80. Fibroblast-activating protein (FAP), preferably human FAP having the amino acid sequence of SEQ ID NO: 1 or its homolog, interacting with 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, 4 A compound according to any one of claims 2, 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, and 79, wherein the amino acid sequence of the homolog has at least 85% identity with the amino acid sequence of SEQ ID NO: 1. Embodiment 81. The compound described in Embodiment 80, which is an inhibitor of fibroblast-activating protein (FAP). Embodiment 82. 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, wherein the pIC50 value of SEQ ID NO: 1 for human FAP is 6.0 or higher, preferably 7.0 or higher, and most preferably 8.0 or higher. A compound according to any one of the following items: 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, and 81. Embodiment 83. 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, for use in a method for diagnosing diseases. A compound according to any one of the following items: 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, and 82. Embodiment 84. The disease is a disease in which the upregulated expression of fibroblast-activating protein (FAP), preferably fibroblast-activating protein (FAP), is involved. Compounds for use as described in Form 83. Embodiment 85. The compound for use according to any one of Embodiments 83 to 84, wherein the disease is associated with diseased tissue containing cells exhibiting upregulated expression of fibroblast-activating protein (FAP), preferably cells exhibiting upregulated expression of fibroblast-activating protein (FAP), and more preferably a tumor-associated fibroblast-related disease. Embodiment 86. The compound for use according to any one of Embodiments 83 to 85, wherein the disease is a neoplasm, preferably cancer or a tumor. Embodiment 87. The compound for use according to Embodiment 86, wherein the neoplasm, cancer, and tumor are individually selected from the group including solid tumors, epithelial tumors, bladder cancer, breast cancer, cervical cancer, colorectal cancer, bile duct cancer, endometrial cancer, esophageal cancer, gastric cancer, gastrointestinal stromal tumors, head and neck cancer, liver cancer, lung cancer, melanoma, mesothelioma, neuroendocrine tumors and carcinomas, ovarian cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, salivary gland cancer, sarcoma, squamous cell carcinoma, and thyroid cancer. Embodiment 88. The compound for use according to Embodiment 87, wherein the neoplasm, cancer, and tumor are individually selected from the group including breast cancer, colorectal cancer, cholangiocarcinoma, head and neck cancer, lung cancer, mesothelioma, neuroendocrine tumors and carcinomas, ovarian cancer, pancreatic cancer, prostate cancer, sarcoma, and squamous cell carcinoma. Embodiment 89. The compound for use according to any one of Embodiments 83 to 85, wherein the disease is selected from the group including inflammatory diseases, cardiovascular diseases, autoimmune diseases, and fibrotic diseases. Embodiment 90. The compound for use according to Embodiment 89, wherein the disease is an inflammatory disease. Embodiment 91. The compound for use according to Embodiment 90, wherein the disease is atherosclerosis, arthritis, or rheumatoid arthritis. Embodiment 92. The compound for use according to Embodiment 91, wherein the disease is a cardiovascular disease. Embodiment 93. The compound for use according to Embodiment 92, wherein the disease is a cardiovascular disease involving atherosclerotic plaques. Embodiment 94. The compound for use according to Embodiment 93, wherein the disease is an atherosclerotic lesion caused by plaque destruction, acute coronary insufficiency syndrome, myocardial infarction, thrombosis, or vascular occlusion. Embodiment 95. The compound for use according to Embodiment 83, wherein the disease is a fibrous disease. Embodiment 96. The compound for use according to Embodiment 95, wherein the disease is selected from the group including idiopathic pulmonary fibrosis, Crohn's disease, and hepatic fibrosis. Embodiment 97. A compound for use according to any one of Embodiments 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, and 96, comprising a diagnostically active nuclide, preferably a diagnostically active radionuclide. Embodiment 98. The diagnostically active nuclide is 43 Sc, 44 Sc, 51 Mn, 52 Mn, 64 Cu, 67 Ga, 68 Ga, 86Y, 89 Zr, 94m Tc, 99m Tc, 111 In, 152 Tb, 155 Tb, 201 Tl, 203 Pb, 18 F, 76 Br, 77 Br, 123 I, 124 I, 125 I, preferably 43 Sc, 44 Sc, 64 Cu, 67 Ga, 68 Ga, 86 Y, 89 Zr, 99m Tc, 111 In, 152 Tb, 155 Tb, 203 Pb, 18 F, 76 Br, 77 Br, 123 I, 124 I, 125 I, Comfort 64 Cu, 68 Ga, 89 Zr, 99m Tc, 111 In, 18 F, 123 I, and 124 A compound for use according to Embodiment 97, selected from the group including I. Embodiment 99. The compound for use according to any one of Embodiments 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, and 98, wherein the method for diagnosis is an imaging method. Embodiment 100. The imaging method is selected from the group consisting of scintigraphy, single-photon emission computed tomography (SPECT), and positron emission tomography (PET). , the compound for use as described in Embodiment 98. Embodiment 101. The compound for use according to any one of Embodiments 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, and 100, wherein the method comprises the step of administering a diagnostically effective amount of the compound to a subject, preferably a mammal, wherein the mammal is selected from the group including humans, companion animals, pets, and livestock, more preferably the subject is selected from the group including humans, dogs, cats, horses, and cattle, and most preferably the subject is human. Embodiment 102. 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, for use in a method for treating a disease. A compound according to any one of the following items: 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, and 82. Embodiment 103. The compound for use according to Embodiment 102, wherein the disease is a disease involving the upregulated expression of fibroblast-activating protein (FAP), preferably fibroblast-activating protein (FAP). Embodiment 104. The compound for use according to any one of Embodiments 102 to 103, wherein the disease is associated with affected tissue containing cells exhibiting upregulated expression of fibroblast-activating protein (FAP), preferably cells exhibiting upregulated expression of fibroblast-activating protein (FAP), and more preferably a disease involving tumor-associated fibroblasts. Embodiment 105. The compound for use according to any one of Embodiments 102 to 104, wherein the disease is a neoplasm, preferably cancer or a tumor. Embodiment 106. The compound for use according to Embodiment 105, wherein the neoplasm, cancer, and tumor are individually selected from the group including solid tumors, epithelial tumors, bladder cancer, breast cancer, cervical cancer, colorectal cancer, bile duct cancer, endometrial cancer, esophageal cancer, gastric cancer, gastrointestinal stromal tumors, head and neck cancer, liver cancer, lung cancer, melanoma, mesothelioma, neuroendocrine tumors and carcinomas, ovarian cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, salivary gland cancer, sarcoma, squamous cell carcinoma, and thyroid cancer. Embodiment 107. The compound for use according to Embodiment 106, wherein the neoplasm, cancer, and tumor are individually selected from the group including breast cancer, colorectal cancer, cholangiocarcinoma, head and neck cancer, lung cancer, mesothelioma, neuroendocrine tumors and carcinomas, ovarian cancer, pancreatic cancer, prostate cancer, sarcoma, and squamous cell carcinoma. Embodiment 108. The compound for use according to any one of Embodiments 102, 103, and 104, wherein the disease is selected from the group including inflammatory diseases, cardiovascular diseases, autoimmune diseases, and fibrotic diseases. Embodiment 109. The compound for use according to Embodiment 108, wherein the disease is an inflammatory disease. Embodiment 110. The compound for use according to Embodiment 109, wherein the disease is atherosclerosis, arthritis, or rheumatoid arthritis. Embodiment 111. The compound for use according to Embodiment 108, wherein the disease is a cardiovascular disease. Embodiment 112. The compound for use according to Embodiment 111, wherein the disease is a cardiovascular disease involving atherosclerotic plaques. Embodiment 113. The compound for use according to Embodiment 112, wherein the disease is an atherosclerotic lesion caused by plaque destruction, acute coronary insufficiency syndrome, myocardial infarction, thrombosis, or vascular occlusion. Embodiment 114. The compound for use according to Embodiment 108, wherein the disease is a fibrous disease. Embodiment 115. The disease is a group that includes idiopathic pulmonary fibrosis, Crohn's disease, and hepatic fibrosis. A compound selected for use according to Embodiment 114. Embodiment 116. A compound for use according to any one of Embodiments 102, 103, 104, and 105, comprising a therapeutically active nuclide, preferably a therapeutically active radionuclide. Embodiment 117. The therapeutically active radionuclide 47 Sc, 67 Cu, 89 Sr, 90 Y, 153 Sm, 149 Tb, 161 Tb, 177 Lu, 186 Re, 188 Re, 212 Pb, 213 Bi, 223 Ra, 225 Ac, 226 Th, 227 Th, 131 I, 211 At, preferably 47 Sc, 67 Cu, 90 Y, 177 Lu, 188 Re, 212 Pb, 213 Bi, 225 Ac, 227 Th, 131 I, 211 At, most preferably 90 Y, 177 Lu, 225 Ac, 227 Th, 131 I, and 211 A compound for use according to Embodiment 116, selected from the group including At. Embodiment 118. The compound for use according to any one of Embodiments 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, and 117, wherein the method comprises the step of administering a therapeutically effective amount of the compound to a subject, preferably a mammal, wherein the mammal is selected from the group including humans, companion animals, pets, and livestock, more preferably the subject is selected from the group including humans, dogs, cats, horses, and cattle, and most preferably the subject is human. Embodiment 119. 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 for use in a method for identifying a target. A compound according to any one of claims 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, and 82, wherein the subject is likely to respond to treatment of the disease or is likely not to respond, and the method for identifying the subject is 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 A method of diagnosis using a compound described in any one of claims 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, and 82, preferably comprising the step of performing a method for diagnosing a disease described in any one of embodiments 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, and 101. Embodiment 120. 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 for use in a method for selecting a target from a group of targets. , 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, and 82 A compound described in any one of the claims, wherein the subject is likely to respond to treatment of the disease or is likely not to respond, and the method for selecting a subject from the group of subjects is, 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, 6 A method of diagnosis using a compound described in any one of claims 9, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, and 82, preferably comprising the step of performing a method for diagnosing a disease described in any one of embodiments 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, and 101. Embodiment 113. 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 for use in a method for stratifying a group of subjects into those likely to respond to disease treatment and those not likely to respond to disease treatment. A compound according to any one of claims 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, and 82, wherein the method for stratifying the target group is 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 A method of diagnosis using a compound described in any one of claims 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, and 82, preferably comprising the step of performing a method for diagnosing a disease described in any one of embodiments 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, and 101. Embodiment 122. The compound for use according to any one of Embodiments 119, 120, and 121, wherein the disease is a disease involving the upregulated expression of fibroblast-activating protein (FAP), preferably fibroblast-activating protein (FAP). Embodiment 123. The compound for use according to any one of Embodiments 119, 120, 121, and 122, wherein the disease is associated with diseased tissue containing cells exhibiting upregulated expression of fibroblast-activating protein (FAP), preferably cells exhibiting upregulated expression of fibroblast-activating protein (FAP), and more preferably a tumor-associated fibroblast-related disease. Embodiment 124. The compound for use according to any one of Embodiments 119, 120, 121, 122, and 123, wherein the disease is a neoplasm, preferably cancer or a tumor. Embodiment 125. The compound for use according to Embodiment 124, wherein the neoplasm, cancer, and tumor are individually selected from the group including solid tumors, epithelial tumors, bladder cancer, breast cancer, cervical cancer, colorectal cancer, bile duct cancer, endometrial cancer, esophageal cancer, gastric cancer, gastrointestinal stromal tumors, head and neck cancer, liver cancer, lung cancer, melanoma, mesothelioma, neuroendocrine tumors and carcinomas, ovarian cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, salivary gland cancer, sarcoma, squamous cell carcinoma, and thyroid cancer. Embodiment 126. The compound for use according to Embodiment 125, wherein the neoplasm, cancer, and tumor are individually selected from the group including breast cancer, colorectal cancer, cholangiocarcinoma, head and neck cancer, lung cancer, mesothelioma, neuroendocrine tumors and carcinomas, ovarian cancer, pancreatic cancer, prostate cancer, sarcoma, and squamous cell carcinoma. Embodiment 127. The compound for use according to any one of Embodiments 119, 120, 121, 122, and 123, wherein the disease is selected from the group including inflammatory diseases, cardiovascular diseases, autoimmune diseases, and fibrotic diseases. Embodiment 128. The compound for use according to Embodiment 127, wherein the disease is an inflammatory disease. Embodiment 129. The disease is atherosclerosis, arthritis, or rheumatoid arthritis. The compound for use as described in Embodiment 128. Embodiment 130. The compound for use according to Embodiment 129, wherein the disease is a cardiovascular disease. Embodiment 131. The compound for use according to Embodiment 130, wherein the disease is a cardiovascular disease involving atherosclerotic plaques. Embodiment 132. The compound for use according to Embodiment 131, wherein the disease is an atherosclerotic lesion caused by plaque destruction, acute coronary insufficiency syndrome, myocardial infarction, thrombosis, or vascular occlusion. Embodiment 133. The compound for use according to Embodiment 127, wherein the disease is a fibrous disease. Embodiment 134. The compound for use according to Embodiment 1335, wherein the disease is selected from the group including idiopathic pulmonary fibrosis, Crohn's disease, and hepatic fibrosis. Embodiment 135. The compound for use according to any one of Embodiments 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, and 134, wherein the diagnostic method is an imaging method. Embodiment 136. The compound for use according to Embodiment 135, wherein the imaging method is selected from the group including scintigraphy, single-photon emission computed tomography (SPECT), and positron emission tomography (PET). Embodiment 137. A compound for use according to any one of Embodiments 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, and 136, comprising a diagnostically active nuclide, preferably a diagnostically active radionuclide. Embodiment 138. The diagnostically active nuclide is 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, 201 Tl, 203 Pb,18 F, 76 Br, 77 Br, 123 I, 124 I, 125 I, preferably 43 Sc, 44 Sc, 64 Cu, 67 Ga, 68 Ga, 86 Y, 89 Zr, 99m Tc, 111 In, 152 Tb, 155 Tb, 203 Pb, 18 F, 76 Br, 77 Br, 123 I, 124 I, 125 I, most preferably 64 Cu, 68 Ga, 89 Zr, 99m Tc, 111 In, 18 F, 123 I, and 124 A compound for use according to Embodiment 137, selected from the group including I. Embodiment 139. 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, for use in a method for delivering an effector to fibroblast-activating protein (FAP), preferably human fibroblast-activating protein (FAP). A compound according to any one of claims 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, and 82, wherein the effector is selected from the group comprising diagnostically active agents and therapeutically active agents. Embodiment 140. The compound for use according to Embodiment 139, wherein the effector is selected from the group comprising diagnostically active and therapeutically active radionuclides. Embodiment 141. The compound for use according to Embodiment 140, wherein the diagnostically active nuclide is a diagnostically active radionuclide. Embodiment 142. The diagnostically active radionuclide is 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, 201 Tl, 203 Pb, 18 F, 76 Br, 77 Br, 123 I, 124 I, 125 I, preferably 43 Sc, 44 Sc, 64 Cu, 67 Ga, 68 Ga, 86 Y, 89 Zr, 99m Tc, 111 In, 152 Tb, 155 Tb, 203 Pb, 18 F, 76 Br, 77 Br, 123 I, 124 I, 125 I, most good Mashiku 64 Cu, 68 Ga, 89 Zr, 99m Tc, 111 In, 18 F, 123 I, and 124 A compound for use according to Embodiment 141, selected from the group consisting of I. Embodiment 143. The compound for use according to any one of Embodiments 139, 140, 141, and 142, wherein the fibroblast-activating protein (FAP) is expressed by cells, preferably fibroblasts, mesenchymal stem cells, smooth muscle cells, epithelial-derived cells, or endothelial cells, more preferably human fibroblasts, mesenchymal stem cells, smooth muscle cells, epithelial-derived cells, or endothelial cells, most preferably human fibroblasts, mesenchymal stem cells, smooth muscle cells, epithelial-derived cells, or endothelial cells, each exhibiting upregulated expression of fibroblast-activating protein (FAP). Embodiment 144. The compound for use according to Embodiment 143, wherein the cells are contained in or part of a tissue, preferably a diseased tissue of a diseased subject. Embodiment 145. The compound for use according to Embodiment 144, wherein the disease is associated with a diseased tissue containing cells exhibiting upregulated expression of fibroblast-activating protein (FAP), preferably cells exhibiting upregulated expression of fibroblast-activating protein (FAP), and more preferably a tumor-associated fibroblast-related disease. Embodiment 146. The compound for use according to any one of Embodiments 144 to 145, wherein the disease is a neoplasm, preferably cancer or a tumor. Embodiment 147. The compound for use according to Embodiment 146, wherein the neoplasm, cancer, and tumor are individually selected from the group including solid tumors, epithelial tumors, bladder cancer, breast cancer, cervical cancer, colorectal cancer, bile duct cancer, endometrial cancer, esophageal cancer, gastric cancer, gastrointestinal stromal tumors, head and neck cancer, liver cancer, lung cancer, melanoma, mesothelioma, neuroendocrine tumors and carcinomas, ovarian cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, salivary gland cancer, sarcoma, squamous cell carcinoma, and thyroid cancer. Embodiment 148. The compound for use according to Embodiment 147, wherein the neoplasm, cancer, and tumor are individually selected from the group including breast cancer, colorectal cancer, cholangiocarcinoma, head and neck cancer, lung cancer, mesothelioma, neuroendocrine tumors and carcinomas, ovarian cancer, pancreatic cancer, prostate cancer, sarcoma, and squamous cell carcinoma. Embodiment 149. The compound for use according to any one of Embodiments 144 to 145, wherein the disease is selected from the group including inflammatory diseases, cardiovascular diseases, autoimmune diseases, and fibrotic diseases. Embodiment 150. The compound for use according to Embodiment 149, wherein the disease is an inflammatory disease. Embodiment 151. The compound for use according to Embodiment 150, wherein the disease is atherosclerosis, arthritis, or rheumatoid arthritis. Embodiment 152. The compound for use according to Embodiment 149, wherein the disease is a cardiovascular disease. Embodiment 153. The compound for use according to Embodiment 152, wherein the disease is a cardiovascular disease involving atherosclerotic plaques. Embodiment 154. The compound for use according to Embodiment 153, wherein the disease is an atherosclerotic lesion caused by plaque destruction, acute coronary insufficiency syndrome, myocardial infarction, thrombosis, or vascular occlusion. Embodiment 155. The compound for use according to Embodiment 149, wherein the disease is a fibrous disease. Embodiment 156. The compound for use according to Embodiment 155, wherein the disease is selected from the group including idiopathic pulmonary fibrosis, Crohn's disease, and hepatic fibrosis. Embodiment 157. The compound for use according to Embodiment 140, wherein the therapeutically active nuclide is a therapeutically active radionuclide. Embodiment 158. The therapeutically active radionuclide is 47 Sc, 67 Cu, 89 Sr, 90 Y, 153 Sm, 149 Tb, 161 Tb, 177 Lu, 186 Re, 188 Re, 212 Pb, 213 Bi, 223 Ra, 225 Ac, 226 Th, 227 Th, 131 I, 211At, preferably 47 Sc, 67 Cu, 90 Y, 177 Lu, 188 Re, 212 Pb, 213 Bi, 225 Ac, 227 Th, 131 I, 211 At, most preferably 90 Y, 177 Lu, 225 Ac, 227 Th, 131 I, and 211 A compound for use according to Embodiment 157, selected from the group consisting of At. Embodiment 159. The compound for use according to any one of Embodiments 157 to 158, wherein the fibroblast-activating protein (FAP) is expressed by cells, preferably fibroblasts, mesenchymal stem cells, smooth muscle cells, epithelial-derived cells, or endothelial cells, more preferably human fibroblasts, mesenchymal stem cells, smooth muscle cells, epithelial-derived cells, or endothelial cells, most preferably human fibroblasts, mesenchymal stem cells, smooth muscle cells, epithelial-derived cells, or endothelial cells exhibiting upregulated expression of fibroblast-activating protein (FAP). Embodiment 160. The compound for use according to Embodiment 159, wherein the cells are contained in or part of tissue, preferably diseased tissue of a diseased subject. Embodiment 161. The compound for use according to Embodiment 160, wherein the disease is associated with diseased tissue containing cells exhibiting upregulated expression of fibroblast-activating protein (FAP), preferably cells exhibiting upregulated expression of fibroblast-activating protein (FAP), and more preferably a tumor-associated fibroblast-related disease. Embodiment 162. The compound for use according to any one of Embodiments 159, 160, and 161, wherein the disease is a neoplasm, preferably cancer or a tumor. Embodiment 163. The compound for use according to Embodiment 162, wherein the neoplasm, cancer, and tumor are individually selected from the group including solid tumors, epithelial tumors, bladder cancer, breast cancer, cervical cancer, colorectal cancer, bile duct cancer, endometrial cancer, esophageal cancer, gastric cancer, gastrointestinal stromal tumors, head and neck cancer, liver cancer, lung cancer, melanoma, mesothelioma, neuroendocrine tumors and carcinomas, ovarian cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, salivary gland cancer, sarcoma, squamous cell carcinoma, and thyroid cancer. Embodiment 164. 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, 5 A composition comprising any one of the compounds described in 1, 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, and 82, and a pharmaceutically acceptable excipient, preferably a pharmaceutical composition. Embodiment 165. The composition according to Embodiment 164 for use in any method defined in any of the prior claims. Embodiment 166. A method for diagnosing a disease in a subject, wherein a diagnostically effective amount 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, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43 A method comprising the step of administering a compound described in any one of the following items: 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, and 82 to the subject. Embodiment 167. The method according to Embodiment 166, wherein the compound comprises a diagnostically active agent, and the agent is preferably a radionuclide. Embodiment 168. A method for treating a disease in a subject, wherein the therapeutically effective amount is 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, 3 8, 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, and 82 A method comprising the step of administering a compound described in any one of the items to the subject. Embodiment 169. The method according to Embodiment 168, wherein the compound comprises a therapeutically active agent, and the agent is preferably a radionuclide. Embodiment 170. The method according to any one of Embodiments 166, 167, 168, and 169, wherein the disease is a disease involving the upregulated expression of fibroblast-activating protein (FAP), preferably fibroblast-activating protein (FAP). Embodiment 171. The method according to any one of Embodiments 166, 167, 168, 169, and 170, wherein the disease is associated with diseased tissue containing cells exhibiting upregulated expression of fibroblast-activating protein (FAP), preferably cells exhibiting upregulated expression of fibroblast-activating protein (FAP), and more preferably a disease involving tumor-associated fibroblasts. Embodiment 172. The method according to any one of Embodiments 166, 167, 168, 169, 170, and 171, wherein the disease is selected from the group including neoplasms, preferably cancer or tumors, and inflammatory diseases, cardiovascular diseases, autoimmune diseases, and fibrotic diseases. Embodiment 173. 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, 6 A kit comprising a compound according to any one of claims 6, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, and 82, one or more excipients as needed, and one or more devices as needed, wherein the devices are selected from the group comprising labeling devices, purification devices, handling devices, radiation protection devices, analytical devices, or administration devices. Embodiment 174. The kit according to Embodiment 173 for use in any method defined in any of the prior claims.

[0411] More specifically, the problem underlying the present invention is, in the first embodiment, Equation (I)

[0412] [ka]

[0413] cyclic peptide and a compound comprising an N-terminal modification group A bonded to Xaa1, The aforementioned peptide sequence is drawn from left to right in the direction from the N-terminus to the C-terminus. Xaa1 is equation (II).

[0414] [ka]

[0415] It is a residue of the amino acid, R 1a is -NH-, R 1b is H or CH3, n=0 or 1, The aforementioned N-terminal modification group A is covalently bonded to the nitrogen atom of Xaa1, The carbonyl group of Xaa1 is covalently bonded to the nitrogen of Xaa2. The sulfur atom of Xaa1 is covalently bonded to Yc as a thioether. Xaa2 is equation (III), (IV), or (XX)

[0416] [ka]

[0417] It is a residue of the amino acid, R 2a , R 2b , R 2c Each of these is independently selected from the group consisting of (C1-C2) alkyl and H, and the (C1-C2) alkyl may be substituted with a substituent selected from the group consisting of OH, NH2, halogen, and (C5-C7) cycloalkyl. p = 0, 1, or 2, v=1 or 2, w = 1, 2, or 3, The amino acid of formula (IV) may be substituted at positions 3 and 4 of the indicated ring with one or two substituents selected from the group consisting of methyl, OH, NH2, and F. Xaa3 is expression (V) or (XX)

[0418] [ka]

[0419] It is a residue of the amino acid, X3 CH2, CF2, CH-R 3b Selected from the group consisting of S, O, and NH, p=1 or 2, v=1 or 2, w = 1, 2, or 3, R 3a is H, methyl, OH, NH2, or F, R 3b is methyl, OH, NH2, or F, Xaa4 is equation (VI).

[0420] [ka]

[0421] It is a residue of the amino acid, R 4a H, OH, COOH, CONH2, X 4 , and -NH-CO-X 4 Selected from the group consisting of X 4 X is selected from the group consisting of (C1-C6) alkyl, (C5-C6) aryl, and (C5-C6) heteroaryl, 4 It may be substituted with one or two substituents selected from the group consisting of methyl, CONH2, halogen, NH2, and OH. q = 1, 2, or 3, and one or two hydrogens of the one, two, or three CH2- groups are optionally substituted individually with methyl, ethyl, (C5-C6)aryl, or (C5-C6)heteroaryl groups. R 4b is methyl or H, Xaa5 structure (VII)

[0422] [ka]

[0423] It is a residue of the amino acid, R 5The group selected is from the OH and NH2 groups. r = 1, 2, or 3, Xaa6 is an amino acid selected from the group consisting of aromatic L-α-amino acids and heteroaromatic L-α-amino acids. Xaa7 is equation (IX).

[0424] [ka]

[0425] It is an aminothiol or amino acid residue, R 7a -CO-, -COOH, -CONH2, -CH2-OH, -(CO)-NH-R 7b ,-(CO)-(NR 7c )-R 7b , or H, R 7b and R 7c Each of them is independently a (C1-C4) alkyl, t is 1 or 2, Yc is given by equation (X).

[0426] [ka]

[0427] The structure is such that the sulfur atom of Xaa1 and the sulfur atom of Xaa7 are linked under the formation of two thioether linkages, thereby forming equation (XXI)

[0428] [ka]

[0429] It forms a ring structure, The substitution pattern of the aromatic group in formula (X) is ortho, meta, or para. n=0 or 1, t=1 or 2, Y 1 is CH or N, Y2 is N or CR c1 And, R c1 is H or CH2-R c2 And, R c2 is equation (XI), (XII), or (XXII)

[0430] [ka]

[0431] It has the following structure: R c3 and R c4 Each is independently selected from the group consisting of H and (C1-C4) alkyl groups, u = 1, 2, 3, 4, 5, or 6, x and y are independently 1, 2, or 3. X = O or S In equations (XI) and (XXII), one of the nitrogen atoms is R c1 It is bonded to -CH2- and in equation (XII) -X- is R c1 -CH2- is bonded, The N-terminal modification group A is a blocking group Abl or an amino acid Aaa. This is resolved by compounds.

[0432] More specifically, in a second embodiment, the underlying problem of the present invention is solved by the compounds described in the first embodiment, including any embodiment for use in a method for diagnosing a disease. .

[0433] More specifically, in a third embodiment, the underlying problem of the present invention is solved by the compounds described in the first embodiment, including any embodiment for use in methods for treating diseases.

[0434] More specifically, in a fourth embodiment, the underlying problem of the present invention is solved by a compound according to the first embodiment, including any embodiment, for use in a method for identifying a subject, wherein the subject is likely to respond to treatment for a disease or is likely not to respond, and the method for identifying a subject includes the step of performing a diagnostic method using a compound according to the first embodiment, including any embodiment.

[0435] More specifically, in a fifth embodiment, the underlying problem of the present invention is a method for selecting subjects from a population of subjects, wherein the subjects are likely to respond to treatment for a disease or are likely not to respond, and the method for selecting subjects from a population of subjects is solved by a compound described in a first embodiment, including any embodiment, for use in a method, the method comprising the step of performing a diagnostic method using a compound described in a first embodiment, including any embodiment.

[0436] More specifically, in a sixth embodiment, the problem underlying the present invention is a method for stratifying a population of subjects into subjects likely to respond to treatment for a disease and subjects unlikely to respond to treatment for a disease, wherein the method for stratifying subjects is solved by a compound according to the first embodiment, including any embodiment, for use in a method, the method comprising the step of performing a diagnostic method using a compound according to the first embodiment, including any embodiment.

[0437] More specifically, in the seventh embodiment, the underlying problem of the present invention is solved by a composition comprising the compound described in the first embodiment, including any embodiment, a pharmaceutically acceptable excipient, preferably a pharmaceutical composition.

[0438] More specifically, in the eighth embodiment, the problem underlying the present invention is solved by a method for diagnosing a disease in a subject, the method comprising the step of administering to the subject a diagnostically effective amount of a compound described in the first embodiment, including any embodiment.

[0439] More specifically, in the ninth embodiment, the underlying problem of the present invention is solved by a method for treating a disease in a subject, the method comprising the step of administering a therapeutically effective amount of the compound described in the first embodiment, including any embodiment, to the subject.

[0440] More specifically, in a tenth embodiment, the underlying problem of the present invention is solved by a kit comprising a compound described in a first embodiment, including any embodiment, one or more optional excipients, and optionally one or more devices, wherein the devices are selected from the group including labeling devices, purification devices, manipulation devices, radioprotection devices, analytical devices, or administration devices.

[0441] Those skilled in the art will recognize that a compound of the present invention or any compound disclosed herein, including, but not limited to, any compound described in any of the above embodiments and any of the following embodiments.

[0442] Those skilled in the art will recognize that a certain method of the present invention or any method disclosed herein includes, but is not limited to, any method described in any of the above embodiments and any of the following embodiments.

[0443] Those skilled in the art will recognize that a certain composition of the present invention or any composition disclosed herein includes, but is not limited to, any composition described in any of the above embodiments and any of the following embodiments.

[0444] Those skilled in the art will recognize that a certain kit of the present invention or any kit disclosed herein includes, but is not limited to, any kit described in any of the above embodiments and any of the following embodiments.

[0445] Since no nanomolar affinity-specific cyclic peptide-based inhibitors for fibroblast-activating proteins (FAPs) have been described to date, the present invention is based on the inventors' remarkable discovery that the compound of the present invention, more specifically its cyclic peptide, provides highly specific binding to FAPs for compounds containing such cyclic peptides.

[0446] Furthermore, the present invention is based on the remarkable discovery that chelating agents can be attached to the cyclic peptide directly or indirectly, i.e., using linkers, at three different positions. The first position is Yc having the structure of formula (X), linking the S atom of Xaa1 to the S atom of Xaa7, and thus forming two thioether linkages; the second position is Aaa attached to Xaa1 of the cyclic peptide of formula (I); and the third position is an amino acid or peptide attached to Xaa7. Remarkably, such attachment of chelating agents does not significantly affect the binding of the compounds of the present invention to FAP, or the inhibitory properties of the compounds of the present invention to FAP. In one embodiment, the present invention relates to a cyclic peptide of formula (I) in which the chelating agent (Z group) is attached to only one of the first, second, or third positions defined above. It is also within the scope of the present invention that the chelating agent is attached to the cyclic peptide of formula (I) in any combination of the first, second, and third positions defined above. More specifically, the present invention also relates to compounds of formula (I) in which the Z group is attached to both the first and second positions defined above, compounds of formula (I) in which the Z group is attached to both the first and third positions defined above, compounds of formula (I) in which the Z group is attached to both the second and third positions defined above, and compounds of formula (I) in which the Z group is attached to the first, second and third positions defined above. These compounds containing two or three Z groups can be realized in any embodiment of the present invention disclosed herein.

[0447] Finally, the inventors found that the compounds of the present invention are remarkably stable in plasma, remarkably useful as imaging agents, and effective in shrinking tumors. As is preferred herein, the term “alkyl” refers, each and independently, to a saturated, linear, or branched hydrocarbon group, usually accompanied by a modifier specifying the number of carbon atoms it may contain. For example, the expression (C1-C6) alkyl means, each and independently, 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 any other isoform of alkyl groups containing six saturated carbon atoms.

[0448] In some embodiments, preferably as used herein, (C1-C2)alkyl means either methyl or ethyl, respectively and independently. In some embodiments, preferably as used herein, (C1-C3)alkyl means methyl, ethyl, n-propyl, and isopropyl, respectively and independently.

[0449] In some embodiments, and preferably as used herein, (C1-C4) "Kil" refers to any of the following: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and tert-butyl.

[0450] In some embodiments, preferably as used herein, (C1-C6) alkyl groups are, respectively and independently, 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-methylbuta-2-yl, 2-methylbuta-2-yl, 2,2-dimethylpropyl, n-hexyl, 2-hexyl, 2-methyl -This means any of the following: pentyl, 3-methylpentyl, 4-methylpentyl, 3-hexyl, 2-ethylbutyl, 2-methylpenta-2-yl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 3-methylpenta-2-yl, 4-methylpenta-2-yl, 2,3-dimethylbutyl, 3-methylpenta-3-yl, 2-methylpenta-3-yl, 2,3-dimethylbuta-2-yl, and 3,3-dimethylbuta-2-yl.

[0451] In some embodiments, preferably as used herein, (C1-C8)alkyl refers to a saturated or unsaturated, linear or branched hydrocarbon group having 1 to 8 carbon atoms. Typical (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-buta-2-yl, 2-methyl-buta-2-yl, 2,2-dimethylpropyl, n-hexyl, 2-hexyl, 2-methyl-pentyl, 3-methyl-pentyl, and 4-methyl-pentyl ,3-hexyl,2-ethyl-butyl,2-methyl-penta-2-yl,2,2-dimethyl-butyl,3,3-dimethyl-butyl,3-methyl-penta-2-yl,4-methyl-penta-2-yl,2,3-dimethyl-butyl,3-methyl-penta-3-yl,2-methyl-penta-3-yl,2,3-dimethyl-buta-2-yl,3,3-dimethyl-buta-2-yl,n-heptyl,2-heptyl,2-methylhexyl,3-methylhexyl,4-methyl 2-Heptyl, 5-methylhexyl, 3-heptyl, 2-ethylpentyl, 3-ethylpentyl, 4-heptyl, 2-methylhexa-2-yl, 2,2-dimethyl(dimetyhl)-pentyl, 3,3-dimethyl(dimetyhl)-pentyl, 4,4-dimethyl(dimetyhl)-pentyl, 3-methylhexa-2-yl, 4-methylhexa-2-yl, 5-methylhexa-2-yl, 2,3-dimethylpentyl, 2,4-dimethyl Tyl-pentyl, 3,4-dimethyl-pentyl, 3-methyl-hexa-3-yl, 2-ethyl-2-methyl-butyl, 4-methyl-hexa-3-yl, 5-methyl-hexa-3-yl, 2-ethyl-3-methyl-butyl, 2,3-dimethyl-penta-2-yl, 2,4-dimethyl-penta-2-yl, 3,3-dimethyl-penta-2-yl, 4,4-dimethyl-penta-2-yl, 2,2,3-trimethyl-butyl, 2,3,3-trimethyl-butyl, 2,3,3-Trimethylbuta-2-yl, n-octyl, 2-octyl, 2-methylheptyl, 3-methylheptyl, 4-methylheptyl, 5-methylheptyl, 6-methylheptyl, 3-octyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 4-octyl, 2-propylpentyl, 2-methylhepta-2-yl, 2,2-dimethylhexyl, 3,3-dimethylhexyl, 4,4-dimethylhexyl, 5,5-dimethylhexyl, 3-methylhepta-2-yl, 4-methylhepta-2-yl, 5- Methyl-hepta-2-yl, 6-methyl-hepta-2-yl, 2,3-dimethyl-hexa-1-yl, 2,4-dimethyl-hexa-1-yl, 2,5-dimethyl-hexa-1-yl, 3,4-dimethyl-hexa-1-yl, 3,5-dimethyl-hexa-1-yl, 3,5-dimethyl-hexa-1-yl, 3-methyl-hepta-3-yl, 2-ethyl-2-methyl-1-yl, 3-ethyl-3-methyl-1-yl, 4-methyl-hepta-3-yl, 5-methyl-hepta-3-yl, 6-methyl-hepta-3-yl, 2-ethyl-3-methylpentyl, 2-ethyl-4-methylpentyl, 3-ethyl-4-methylpentyl, 2,3-dimethylhexa-2-yl, 2,4-dimethylhexa-2-yl, 2,5-dimethylhexa-2-yl, 3,3-dimethylhexa-2-yl, 3,4-dimethylhexa-2-yl, 3,5-dimethylhexa-2-yl, 4,4-dimethylhexa-2-yl, 4,5-dimethylhexa-2-yl, 5,5-dimethylhexa-2-yl, 2,2, 3-trimethylpentyl, 2,2,4-trimethylpentyl, 2,3,3-trimethylpentyl, 2,3,4-trimethylpentyl, 2,4,4-trimethylpentyl, 3,3,4-trimethylpentyl, 3,4,4-trimethylpentyl, 2,3,3-trimethylpenta-2-yl, 2,3,4-trimethylpenta-2-yl, 2,4,4-trimethylpenta-2-yl, 3,4,4-trimethylpenta-2-yl, 2 ,2,3,3-tetramethylbutyl, 3,4-dimethylhexa-3-yl, 3,5-dimethylhexa-3-yl, 4,4-dimethylhexa-3-yl, 4,5-dimethylhexa-3-yl, 5,5-dimethylhexa-3-yl, 3-ethyl-3-methylpenta-2-yl, 3-ethyl-4-methylpenta-2-yl, 3-ethyl-hexa-3-yl, 2,2-diethylbutyl, 3-ethyl-3-methylpentyl, 4-ethyl This includes any of the following: -hexa-3-yl, 5-methylhepta-3-yl, 2-ethyl-3-methylpentyl, 4-methylhepta-4-yl, 3-methylhepta-4-yl, 2-methylhepta-4-yl, 3-ethyl-hexa-2-yl, 2-ethyl-2-methylpentyl, 2-isopropylpentyl, 2,2-dimethylhexa-3-yl, 2,2,4-trimethylpenta-3-yl, and 2-ethyl-3-methylpentyl.The (C1-C8)alkyl 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, where each R' is independently selected from -(C1-C8)alkyl and aryl groups.

[0452] As preferred herein, the term “alkylidene” refers to a saturated linear or branched hydrocarbon group in which two substitution sites are identified. Simple alkyl chains in which the two substitution sites are at maximum distance from each other, such as methane-1,1-diyl, ethane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl, and pentane-1,5-diyl, are also called methylene (also known as methane-1,1-diyl), ethylene (also known as ethane-1,2-diyl), propylene (also known as propane-1,3-diyl), butylene (also known as butane-1,4-diyl), and pentylene (also known as pentane-1,5-diyl).

[0453] In one embodiment, preferably as used herein, (C1-C 10Alkylidenes are, individually and independently, methylene, ethane-1,2-diyl, propane-1,3-diyl, propane-1,2-diyl, butane-1,4-diyl, butane-1,3-diyl, butane-1,2-diyl, 2-methyl-propane-1,2-diyl, 2-methyl-propane-1,3-diyl, pentane-1,5-diyl, pentane-1,4-diyl, pentane-1,3-diyl, pentane-1,2-diyl, pentane-2,3-diyl, pen This means any of the following: tan-2,4-diyl, any other isomer having 5 carbon atoms, hexane-1,6-diyl, any other isomer having 6 carbon atoms, heptane-1,7-diyl, any other isomer having 7 carbon atoms, octane-1,8-diyl, any other isomer having 8 carbon atoms, nonane-1,9-diyl, any other isomer having 9 carbon atoms, decane-1,10-diyl, and any other isomer having 10 carbon atoms, preferably (C1-C 10 Alkylidenes are, individually and independently, methylene, ethane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6-diyl, heptane-1,7-diyl, octane-1, It means one of the following: 8-Jiil, Nonan-1,9-Jiil, or Decane-1,10-Jiil. (C1-C 10 The alkylidene 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, where each R' is independently selected from -(C1-C8)alkyl and aryl.

[0454] In some embodiments, preferably as used herein, (C3-C8) cycloalkyl means, each and independently, one of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

[0455] In some embodiments, preferably as used herein, (C5-C7) cycloalkyl means any one of cyclopentyl, cyclohexyl, and cycloheptyl, respectively and independently.

[0456] In some embodiments, preferably as used herein, a (C3-C8) carbocycle refers to a saturated or unsaturated non-aromatic carbocycle with 3, 4, 5, 6, 7, or 8 members. Typical (C3-C8) carbocycles include, but are not limited to, any of -cyclopropyl, -cyclobutyl, -cyclopentyl, -cyclopentadienyl, -cyclohexyl, -cyclohexenyl, -1,3-cyclohexadienyl, -1,4-cyclohexadienyl, -cycloheptyl, -1,3-cycloheptadienyl, -1,3,5-cycloheptatrielinyl, -cyclooctyl, and -cyclooctadienyl. The (C3-C8) carbocyclic group may be unsubstituted, but not limited to, or substituted with one or more groups including (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, where each R' is independently selected from -(C1-C8)alkyl and aryl.

[0457] In some embodiments, preferably as used herein, a (C3-C8)carbocyclo refers to the (C3-C8) carbon ring group as defined above, wherein one of the hydrogen atoms of the carbon ring group is substituted by a bond.

[0458] In some embodiments, and preferably as used herein, “aryl” refers to a carbocyclic aromatic group. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, and anthracenyl.

[0459] In some embodiments, preferably as used herein, (C5-C6)aryl refers to a carbocyclic aromatic group containing five or six carbon atoms. The carbocyclic aromatic group may be unsubstituted or substituted with, 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, where each R' is independently selected from -(C1-C8)alkyl and aryl.

[0460] In some embodiments, preferably as used herein, "heteroaryl" means This refers to heterocyclic aromatic groups. Examples of heteroaryl groups, but are not limited to, include furan, thiophene, pyridine, pyrimidine, benzothiophene, benzofuran, and quinoline.

[0461] In some embodiments, preferably as used herein, a (C5-C6) heteroaryl refers to a heterocyclic aromatic group consisting of 5 or 6 ring atoms, at least one of which is different from carbon, preferably nitrogen, sulfur, or oxygen. The heterocyclic aromatic group may be unsubstituted or substituted with one or more groups, 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, where each R' is independently selected from -(C1-C8)alkyl and aryl.

[0462] In some embodiments, preferably as used herein, a (C3-C8) heterocyclo refers to a (C3-C8) heterocyclic group as defined above, in which one of the hydrogen atoms of the carbocyclic group is substituted by a bond. A (C3-C8) heterocyclo may be unsubstituted or substituted with up to six groups, including (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, where each R' is independently selected from -(C1-C8)alkyl and aryl.

[0463] In one embodiment, preferably as used herein, arylene has two covalent bonds and the following structure:

[0464] [ka]

[0465] As shown, this refers to an aryl group which may be in an ortho, meta, or para configuration, where the phenyl group is unsubstituted or may be substituted with up to four 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, where each R' is independently selected from -(C1-C8)alkyl and aryl.

[0466] In some embodiments, preferably as used herein, an atom having an unspecified atomic mass number in any structural formula or in any context of this specification including the claims is either an unspecified isotopic composition, a naturally occurring mixture of isotopes, or individual isotopes. This includes, in particular, carbon, oxygen, nitrogen, sulfur, phosphorus, halogens, and metal atoms, for example, 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 This applies to Pb, Bi, Po, Fr, Ra, Ac, Th, and Fm.

[0467] In some embodiments, preferably as used herein, the chelating agent is a compound capable of forming a chelate, thereby the chelating agent is a compound, preferably a cyclic compound, in which a metal or portion having an electron gap or lone pair of electrons is involved in ring formation. More preferably, the chelating agent is this type of compound in which a single ligand occupies more than one coordination site at the central atom.

[0468] In some embodiments, preferably as used herein, a diagnostically active compound is a compound suitable for or useful in the diagnosis of a disease. In some embodiments, preferably as used herein, the diagnostic agent or diagnostic activator is a compound suitable or useful for diagnosing a disease.

[0469] In some embodiments, preferably as used herein, a therapeutically active compound is a compound suitable for or useful in treating a disease. In some embodiments, preferably as used herein, the therapeutic agent or therapeutic activator is a compound suitable for or useful in treating a disease.

[0470] In some embodiments, preferably as used herein, a diagnostically and therapeutically active compound is a compound that is suitable or useful for both the diagnosis and treatment of a disease. In some embodiments, preferably as used herein, the diagnostic and therapeutic agent or diagnostic and therapeutic activator is a compound that is suitable or useful for both the diagnosis and treatment of a disease.

[0471] In one embodiment, preferably as used herein, diagnostic-therapeutic is a method for the combined diagnosis and treatment of a disease, and preferably, the combined diagnostic and therapeutically active compounds used in the diagnostic-therapeutic are radiolabeled.

[0472] In some embodiments, as used herein, treatment of a disease is the treatment and / or prevention of a disease. In some embodiments, preferably as used herein, a disease involving FAP is a disease in which cells including fibroblasts expressing FAP, preferably in an upregulated manner, and tissues containing cells such as fibroblasts that express FAP, or express FAP, preferably in an upregulated manner, are one or the sole cause of the disease and / or symptoms of the disease, or are part of the underlying pathology of the disease. Preferred FAP-expressing cells are cancer-associated fibroblasts (CAFs). In embodiments of the disease, preferably as used in connection with the treatment, treatment and / or therapy of the disease, the effects on cells, tissues and pathology, respectively, result in the healing, treatment or improvement of the disease and / or symptoms of the disease. In embodiments of the disease, preferably as used in connection with the diagnosis and / or diagnosis of the disease, the labeling of FAP-expressing cells and / or FAP-expressing tissues can distinguish or differentiate the cells and / or tissues from healthy or non-FAP-expressing cells and / or tissues. More preferably, such identification or distinction forms the basis for the diagnosis and diagnosis described above. In the embodiment, the label means a direct or indirect interaction of the label with FAP-expressing cells and / or FAP-expressing tissue or tissue containing such FAP-expressing cells, and more preferably, such interaction involves or is based on an interaction between the label or a compound having such a label and FAP.

[0473] In some embodiments, preferably as used herein, target cells express FAP and are one or the sole cause of the disease and / or symptoms of the disease, or disease These are cells that are part of the pathology underlying the disease.

[0474] In some embodiments, and preferably as used herein, non-target cells are cells that do not express FAP and / or are not one or the sole cause of the disease and / or symptoms of the disease, or are not part of the pathology underlying the disease.

[0475] In some embodiments, preferably as used herein, a neoplasm is an abnormal new proliferation of cells. Cells in a neoplasm proliferate more rapidly than normal cells and continue to proliferate if left untreated. Neoplasms can be benign or malignant.

[0476] In some embodiments, preferably as used herein, the tumor is a nodular lesion that may be benign or malignant. In some embodiments, preferably as used herein, cancer is a malignant neoplasm.

[0477] In some embodiments, preferably as used herein, a linkage is the attachment of two atoms of two independent parts. A preferred linkage is a chemical bond or a plurality of chemical bonds. More preferably, the chemical bond is a covalent bond or a plurality of chemical bonds. Most preferably, the linkage is a covalent bond or a coordinate bond. Preferably, as used herein, an embodiment with a coordinate bond is a bond or group of bonds realized when metals are bonded by a chelating agent. Different types of linkages are made depending on the types of atoms being linked and their atomic environments. These types of linkages are defined by the type of atomic arrangement made by the linkage. For example, the linkage between a part containing an amine and a part containing a carboxylic acid results in a linkage called an amide linkage (also called an amide linkage, -CO-N-, -N-CO-). Those skilled in the art will recognize that the following examples of making this and linkage are merely prototype examples and do not limit the scope of this application in any way. Those skilled in the art will recognize that the bonding of an amine-containing moiety with an isothiocyanate-containing moiety results in thiourea (also known as thiourea linkage, -N-CS-N-), and the bonding of a C atom-containing moiety with a thiol group (-C-SH) results in thioether (also known as thioether linkage, -CSC-). A non-limiting list of linkages preferably used in connection with the chelating agents and linkers of the present invention, and their characteristic atomic arrangements, are presented in Table 2.

[0478] [Table 2]

[0479] Table 3 summarizes examples of reactive groups used in some embodiments of the present invention to form a linkage between a chelating agent and a linker, or to form a direct bond between a chelating agent and a compound of the present invention. However, it will be understood by those skilled in the art that the linkages that can be realized in embodiments for forming the conjugate of the present invention are not limited to those in Table 3, nor are they limited to the reactive groups that form such linkages.

[0480] [Table 3]

[0481] The following are reactive groups and functional groups used in embodiments of the conjugate of the present invention that are utilized or suitable for forming linkages between parts or structures. Primary or secondary amino acids, carboxylic acids, activated carboxylic acids, chloro, bromo, iodine, sulfhydryl, hydroxyl, sulfonic acid, activated sulfonic acid, sulfonic acid esters such as mesylate or tosylate, Michael acceptors, transcyclooctene, isocyanates, isothiocyanates, azides, alkynes, and strained alkenes such as tetrazines.

[0482] Preferably as 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, the activated form of the carboxylic acid group may include, but is not limited to, acyl chlorides, symmetric or asymmetric anhydrides, and esters. In some embodiments, the activated carboxylic acid group is an ester having pentafluorophenol, nitrophenol, benzotriazole, azabenzotriazole, thiophenol, or N-hydroxysuccinimide (NHS) as the leaving group.

[0483] Preferably as used herein, the term “activated sulfonic acid” refers to a sulfonic acid group having the general formula -SO2-X, where X is a leaving group. For example, the activated form of a sulfonic acid may include, but is not limited to, a sulfonyl chloride or a sulfonic anhydride. In some embodiments, the activated sulfonic acid group is a sulfonyl chloride containing a chloride as the leaving group.

[0484] In some embodiments, preferably as used herein, the term "mediating linkages" "Established" means that a linkage or linkage type is established, preferably a linkage between two parts. In preferred embodiments, the linkage and linkage type are as defined herein.

[0485] In this application, within the range referred to by lower and higher integers, such as 1 to 4, such range is a representation of lower integers, higher integers, and any integer between lower and higher integers. To that extent, this range is in fact an individualized disclosure of the above integers. In the above example, the range 1 to 4 means 1, 2, 3, and 4.

[0486] The compounds of the present invention typically comprise amino acid sequences provided herein. Conventional amino acids, also known as natural amino acids, are identified according to their standard three-letter and one-letter abbreviations, as shown in Table 4.

[0487] [Table 4]

[0488] Non-conventional amino acids, also known as unnatural amino acids, are any type of non-oligomeric compound that contains an amino group and a carboxyl group and is not a conventional amino acid. Examples of non-conventional amino acids and other components used in the constructive compounds of the present invention are identified according to their abbreviations or names found in Table 5. The structures of some components are described by exemplary reagents (e.g., carboxylic acid-like) for introducing the components into peptides, or these components are shown as residues fully attached to another structure, such as a peptide or amino acid. The structures of amino acids are shown as explicit amino acids, and how they are presented after implementation into a peptide sequence is not shown. These are not shown as amino acid residues. Several large chemical parts consisting of more than one component are also shown for clarity.

[0489] [Table 5-1]

[0490] [Table 5-2]

[0491] [Table 5-3]

[0492] [Table 5-4]

[0493] [Table 5-5]

[0494] [Table 5-6]

[0495] [Table 5-7]

[0496] [Table 5-8]

[0497] [Table 5-9]

[0498] [Table 5-10]

[0499] [Table 5-11]

[0500] [Table 5-12]

[0501] [Table 5-13]

[0502] [Table 5-14]

[0503] The amino acid sequences of peptides provided herein are described in a typical peptide sequence format, as can be understood by those skilled in the art. For example, three-letter notations for conventional amino acids, or non-conventional amino acid notations, or abbreviations for additional components indicate the presence of an amino acid or component at a specific position within the peptide sequence. Each amino acid notation or component is connected by a hyphen (typically representing amide linkage) to the next and / or previous amino acid notation or component in the sequence.

[0504] When an amino acid contains more than one amino acid and / or carboxyl group, all orientations of this amino acid are possible in principle, but in the case of α-amino acids, the use of α-amino and α-carboxyl groups is preferred, or otherwise a preferred orientation is explicitly specified.

[0505] For amino acids, the first letter in their abbreviations indicates the stereochemistry of the C-α atom, where applicable. For example, the first capital letter indicates that the L-form of the amino acid is present in the peptide sequence. The presence of the lowercase letter indicates the presence of the D-form of the corresponding amino acid in the peptide sequence.

[0506] In some embodiments, preferably as used herein, the aromatic L-α-amino acid is any type of L-α-amino acid containing an aryl group. In some embodiments, preferably as used herein, the heteroaromatic L-α-amino acid is any type of L-α-amino acid containing a heteroaryl group.

[0507] Those skilled in the art will recognize whether such stereocenters are present in the compounds disclosed herein, whether they are part of an amino acid moiety or any other part or portion of the compounds of the present invention. Therefore, the present invention encompasses both possible stereoisomers, including not only racemic compounds but also individual enantiomers and / or diastereomers. Where a compound is desired as a single enantiomer or diastereomer, it can be obtained by stereospecific synthesis or by the resolution of the final product or any convenient intermediate. The resolution of the final product, intermediate, or starting material can be influenced by any suitable method known in the art. See, for example, "Stereochemistry of Organic Compounds" by ELEEliel, SHWilen, and LNMander (Wiley-Interscience, 1994).

[0508] In this application, the structural formula of a compound may, for convenience, represent certain isomers, but the present invention includes all isomers, such as geometric isomers, optical isomers based on chiral carbons, stereoisomers, and tautomers.

[0509] Unless otherwise specified, amino acid sequences are presented herein from the N-terminus to the C-terminus. Derivatives of amino acids constituting the peptide of the present invention may be listed in Table 6. In any embodiment, one or more amino acids of the compound of the present invention are substituted with a derivative of a corresponding preferred amino acid.

[0510] [Table 6-1]

[0511] [Table 6-2]

[0512] Linear peptides Typical linear peptides are usually described from the N-terminus to the C-terminus, as shown below: NT-Xaa1-Xaa2-Xaa3-Xaa4-...Xaan-CT; There, 1. Xaax is an abbreviation, descriptor, or symbol for an amino acid or component at a specific sequence position x, as shown in Table 5. 2. NT is an abbreviation for the N-terminal group, such as "H" (hydrogen in the case of a free N-terminal amino group), or "Ac" in the case of acetic acid, or another chemical group or structural formula of a chemical group linked to the N-terminal amino acid notation (Xaa1) via a hyphen, and 3. CT is an abbreviation for a C-terminal group that is typically "OH" or "NH2" (as a terminal carboxylic acid or amide), or a specific terminal amine (Xaan) linked to the C-terminal amino acid notation via a hyphen. Branched peptides having side chains modified by specific components or peptides. Typical linear branched peptides are described from the N-terminus to the C-terminus, as shown below: NT-Xaa1-Xaa2-Xaa3(NT-Xab1-Xab2-......Xabn)-......Xaan-CT In this case, the specifications of Xaax, NT, and CT in the main chain of the branched peptide are applied according to the descriptions 1-3 for linear peptides.

[0513] The branching location is specified in parentheses after the abbreviation Xaax. Branching typically occurs at lysine (Lys) residues (or similar), meaning the branching is attached to the ε-amino functional group of the lysine side chain via an amide bond.

[0514] The content in parentheses describes the sequence / structure of the peptide branch "NT-Xab1-Xab2-......Xabn". Here, 1. Xabx is an abbreviation, descriptor, or symbol for an amino acid or component at a specific sequence position x of a branch, as shown in Table 3. 2. NT is the N-terminal group, and for certain terminal carboxylic acids, such as "Ac" in acetic acid, it is an abbreviation or linked to the N-terminal amino acid notation (Xab1) via a hyphen. Other chemical groups or the structural formula of a chemical group, 3. The final component of branched Xabn, which connects the branch to the main chain by forming an amide bond that has the amino function of the lysine (or a similar residue) side chain and its own carboxyl function. Cyclic peptide An exemplary common cyclic peptide described from the N-terminus to the C-terminus is shown below: NT-Xaa1-[Xaa2-Xaa3-Xaa4-......Xaan]-CT; Here, the specifications of Xaax, NT, and CT in the main chain of the cyclic peptide are applied according to explanations 1-3 of the linear peptide description. Characteristics of the peptide cycle are indicated in square brackets.

[0515] 1. Open square brackets indicate the component, which is the side chain (cycle initiation residue) where the cycle begins. 2. Closed square brackets indicate the component, which is the side chain where the cycle ends (cycle termination residue).

[0516] The chemical properties of the connection between these two residues are as follows: 1. An amide bond in which one of the indicated residues contains an amino functional group (e.g., Lys) in its side chain, while the other contains a carboxyl functional group (e.g., Glu) in its side chain, or 2. Disulfide bond when the indicated residue / amino acid contains a sulfhydryl moiety (e.g., Cys). Cyclic peptides containing an addition cycloaddition element (Yc) A typical elongated cyclic peptide described from the N-terminus to the C-terminus is shown below: NT-Xaa1-[Xaa2(Yc)-Xaa3-Xaa4-...Xaan]-CT; Here, the specifications of Xaax, NT, and CT in the backbone of the cyclic peptide are applied according to explanations 1-3 of the linear peptide description. Furthermore, Yc is the cyclization element. As with cyclic peptides, the characteristics of the cycle are identified by square brackets indicating the cycle start and cycle end residues.

[0517] The parentheses adjacent to the cycle start residue identify the cyclization element Yc in the extended peptide cycle. The Yc element is linked to the side chain of the above residue. Furthermore, the Yc element is linked to the side chain of the cycle end residue. The chemical nature of the linkage between any of these residues and the Yc element depends on the side chain functionality of the corresponding amino acid Xaan. If the side chain of Xaan contains a sulfhydryl group (e.g., Cys), the linkage is thioether.

[0518] As a non-restrictive example, the structure of Ac-[Cys(tMeBn(DOTA-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-OH is described below.

[0519] [ka]

[0520] There, 1. Ac corresponds to NT in the general formula. 2. Cys, Pro, Pro, Thr, Gln, Phe, and Cys correspond to Xaa1 to Xaa7 in the general formula.

[0521] 3. OH corresponds to CT in the general formula. 4. Open square brackets (,[') adjacent to the N-terminal cysteine ​​in a sequence indicate that the cycle begins at this residue (cycle start residue).

[0522] 5. Closed square brackets (,]') adjacent to the N-terminal cysteine ​​in a sequence indicate that the cycle ends at this residue (cycle termination residue). 6. The tMeBn in parentheses adjacent to the Cys residue, indicated as the start residue, identifies the cyclization element Yc. It further binds to the Cys residue, indicated as the end-cycle residue. The Yc element is linked to the above residue via a thioether linkage.

[0523] 7. The remaining connection points of the tMeBn residue are chelated by the DOTA chelator via the PP linker. Clear terminology such as "Cys(tMeBn(DOTA-PP))" is included in the list of chemical structures in Table 2.

[0524] In embodiments of the present invention, an amino acid or peptide is attached to Xaa7, and most of the amino acids in this peptide are charged or polar, and the net charge of the peptide is -2, -1, 0, +1, or +2.

[0525] In calculating the net charge of a peptide, negatively charged amino acids are those that have acidic groups such as -COOH or -SO3H in their side chains, and their net charge corresponds to the number of acidic groups; for example, Asp or Glu have a net charge of -1.

[0526] In this calculation, positively charged amino acids are those that have a basic group such as amino or -guanidino in their side chain, and their net charge corresponds to the number of basic groups; for example, Lys or Arg have a net charge of +1.

[0527] Polar amino acids are amino acids that have polar groups in their side chains. Polar groups include CONH2, OH, F, Cl, CN, and heterocyclic groups such as imidazole in histidine. And so on.

[0528] Polar amino acids have a net charge of 0. While some nitrogen-containing heterocycles are known to protonate in equilibrium depending on the pH of the environment and therefore acquire a positive charge to some extent, their net charge is considered to be 0 in calculations.

[0529] Most of the amino acids in this peptide (more than 50%) are charged or polar. Preferably, the positive or negative charge may be determined by polar or nonpolar amino acids.

[0530] In some embodiments, the presence of negatively charged amino acids is preferred in Xaa10. In some embodiments, the presence of positively charged amino acids is preferable for Xaa13, preferably Arg and arg.

[0531] According to the present invention, the compounds of the present invention may contain a Z group. The Z group comprises a chelating agent and optionally a linker. Preferably, when used, a linker is an element, part, or structure that separates two parts of a molecule. In the present invention, the linker group forms a covalent bond with both the chelating agent group and the respective parts of the compound of the present invention to which the Z is attached. The linker group can, in principle, be any chemical group that can form a bond at a particular position with both the chelating agent group and the part of the compound of the present invention.

[0532] An important property or feature of the linker is that it separates the chelating agent and the cyclic peptide moiety of the compound of the present invention. This is particularly important when the target-binding ability of the cyclic peptide is impaired by the proximity of the chelating agent. However, the overall linker length in its most elongated conformational isomer should not exceed 200 Å, preferably 150 Å or less, and most preferably 100 Å or less.

[0533] In a preferred embodiment, the linker is -[X] a -where a is an integer from 1 to 10, and each X is an individual component that is independently connected to its neighbors in the sequence by a functional group selected from those including amide linkages, urea linkages, carbamate linkages, ester linkages, ether linkages, thioether linkages, sulfonamides, triazoles, and disulfide linkages.

[0534] X1 is connected to the chelating agent, and if present, to X2, or to the compound of the present invention at a specific position. a If it exists, then X a-1 It is connected to and connected to the compound of the present invention at a specific position.

[0535] A more preferred class of linker group is -[X] a Represented by -, where a is an integer from 1 to 10, preferably an integer from 1 to 8, 1 to 6, 1 to 5, 1 to 4, or 1 to 3, and each X is an individual component independently connected to its neighbors in the sequence by a functional group selected from the group including amide linkages, urea linkages, carbamate linkages, ester linkages, ether linkages, thioether linkages, sulfonamide linkages, triazole linkages, and disulfide linkages.

[0536] In one embodiment, component X is given by general formula (8)

[0537] [ka]

[0538] It is, and in the formula, If fragments exist, Lin 2 , and fragment Lin if present 3 These are, individually and independently, -CO- and -NR. 10 -, -S-, -CO-NR 10 -, -CS-NR 10 -, -O-, -succinimide and -CH2-CO-NR 10 - Selected from the group including; however, Lin 2 or Lin 3 At least one of them is R having carbon atoms. 9 Linked together, all nitrogen atoms in the nitrogen-containing fragment are R 9 Linked to; R 10 is selected from the group consisting of hydrogen and (C1-C4) alkyl groups; and R 9 is, -(C1-C 10 )alkylidene-,-(C3-C8)carbocyclo-,-arirene-,-(C1-C 10 )Alkyridene-Arirene-,-Arirene-(C1-C 10 )Alkyridene-,-(C1-C 10)Alkyridene-Arirene-(C1-C 10 )Alkyridene-,-(C1-C 10 )alkylidene-(C3-C8)carbocyclo-,-(C3-C8)carbocyclo-(C1-C 10 )Alkyridene-,-(C1-C 10 )alkylidene-(C3-C8)carbocyclo-(C1-C 10 )alkylidene-,-(C3-C8)heterocyclo-,(C1-C 10 )alkylidene-(C3-C8)heterocyclo-,-(C3-C8)heterocyclo-(C1-C 10 )Alkyridene-,-(C1-C 10 )alkylidene-(C3-C8)heterocyclo-(C1-C 10 ) Alkyridene-,-(CH2CH2O) r -, and -(CH2) s -(CH2CH2O) r -(CH2) t - Selected from; r is any integer from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; s is any integer from 0, 1, 2, 3, and 4; t is any integer from 0, 1, 2, 3, and 4.

[0539] Preferably, apart from the linkage between X1 and the chelating agent, the linkage is an amide linkage. More preferably, components X2~X a These are independently selected from the group including amino acids, dicarboxylic acids, and diamines, and their respective linkages are amides.

[0540] In one embodiment, component X2~X aThe amino acid is preferably an amino acid, which is selected from the group including conventional and non-conventional amino acids. In one embodiment, the amino acid is selected from the group including β-amino acids, γ-amino acids, δ-amino acids, ε-amino acids, and ω-amino acids. In a further embodiment, the amino acid is a cyclic amino acid or a linear amino acid. In the case of an amino acid having a chiral center, it will be understood by those skilled in the art that all stereoisomer forms can be used in component X.

[0541] In one embodiment, component X2~X a The amino acid is preferably an amino acid, which is selected from a group of amino acids that differ in the spacing between the carboxyl group and the amino group. These types of amino acids generally include:

[0542] [ka]

[0543] It can be expressed as follows. It is within the scope of the present invention that such amino acids are not further substituted. However, it is also within the scope of the present invention that such amino acids are further substituted, preferably such substitutions are CO-NH2 and / or Ac-NH-.

[0544] Representative examples of this type of amino acid (structure 32) that can be used as component X include glycine (Gly), β-alanine (Bal), γ-aminobutyric acid (GABA), aminopentanoic acid, aminohexanoic acid, and their homologues having up to 10 CH2 groups.

[0545] Typical examples of this type of amino acid (structure 33) that are more preferably used as component X are 3-aminomethylbenzoic acid, 4-aminomethylbenzoic acid, anthranilic acid, 3-aminobenzoic acid, and 4-aminobenzoic acid.

[0546] The relevant components are diamines derived from amino acids (structure 32+33) by substituting NH2 with COOH, which are preferably used as component X and are diaminoethane, 1,3-diaminopropane, 1,4-diaminobutane, 1,5-diaminopentane, 3-aminomethylaniline, 4-aminomethylaniline, 1,2-diaminobenzene, 1,3-diaminobenzene, and 1,4-diaminobenzene.

[0547] The relevant structural units are dicarboxylic acids derived from amino acids (structures 32+33) by substituting COOH with NH2, and those more preferably used as structural unit X are malonic acid, succinic acid, glutaric acid, adipic acid, phthalic acid, terephthalic acid, isophthalic acid, and 2,3 or 4-carboxyphenylacetic acid.

[0548] In further embodiments, the amino acid is preferably an amino acid containing a polyether as a backbone. Preferably, such a polyether is polyethylene glycol and consists of up to 30 monomer units. Preferably, amino acids containing such a polyether exhibit increased hydrophilicity compared to amino acids without such a polyether. Component X, ultimately linker group [X] a When incorporated, this typically results in increased hydrophilicity. Preferred embodiments of this type of amino acid are described below, and such amino acids consist of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 ethylene oxide moieties:

[0549] [ka]

[0550] It is acknowledged that this may include. Preferred ethylene glycols containing amino acids are Ttds(N-(3-{2-[2-[2-(3-amino-propoxy)-ethoxy]-ethoxy}-propyl)-succinic acid) and O2Oc([2-(2-(2-amino-ethoxy)-ethoxy]-acetic acid), whose formulas are as follows:

[0551] [ka]

[0552] In preferred embodiments, the linker comprises an oligomer or monomer of a single specific amino acid selected from the group consisting of Ttds, O2Oc, Apac, Gly, Bal, Gab, Mamb, Pamb, Ppac, 4Amc, Inp, Sni, Rni, Nmg, Cmp, PEG6, PEG12, and PEG-amino acids, and more preferably the linker is a monomer.

[0553] In another preferred embodiment, the linker comprises one component X2 selected from the group of Ttds, O2Oc, Apac, Gly, Bal, Gab, Mamb Pamb, PEG6, PEG12, and PEG-amino acids, and a second component X1 that is directly bonded to the amino-nitrogen of X2 and directly attached to the chelating agent by a linkage selected from the group consisting of amide linkage, urea linkage, carbamate linkage, ester linkage, ether linkage, thioether linkage, sulfonamide, triazole, and disulfide linkage. In this case, X1 acts as an adapter mediating the linkage of different types of attached functional groups provided to the nitrogen atom of amino acid X2 by the chelating agent, in the sense that X1 provides complementary functional groups related to the linkage of the chelating agent.

[0554] However, the use of linkers is usually purposeful. In some situations, it is necessary to leave a larger portion separate from the bioactive molecule in order to maintain high bioactivity. In other situations, the introduction of a linker opens up the opportunity to modify the physicochemical properties of the molecule by introducing polarity or multiple charges. In certain situations, it may be a strength and achievement if a chelating agent can be combined with a bioactive compound without the need for such a linker. In particular, in the compounds of the present invention, where the chelating agent is attached to Yc of formula (X) linking the S atoms of Xaa1 and Xaa7 under the formation of two thioether linkages, excellent performance is typically achieved without the use of any dedicated linker.

[0555] In some embodiments, the compound of the present invention includes a chelating agent. Preferably, the chelating agent is part of the compound of the present invention, thereby being direct or indirect, such as by a linker attached to the compound of the present invention. Preferred chelating agents are those that form a metal chelate comprising at least one radiometal. The at least one radiometal is preferably useful in diagnostic and / or therapeutic and / or diagnostic-therapeutic use, or more preferably useful or suitable for imaging and / or radiotherapy.

[0556] In principle, chelating agents useful and / or suitable for carrying out the present invention, including the diagnosis and / or treatment of diseases, are known to those skilled in the art. A wide variety of each chelating agent is available, for example, Banerjee et al. (Banerjee et al., Dalton) Such chelating agents are outlined in Trans, 2005, Vol. 24: p. 3886, and its references (Price et al., Chem Soc Rev, 2014, Vol. 43: p. 260; Wadas et al., Chem Rev, 2010, Vol. 110: p. 2858). Such chelating agents include, but are not limited to, linear, cyclic, macrocyclic, tetrapyridine, N3S, N2S2, and N4 chelating agents disclosed in U.S. Patents 5,367,080A, 5,364,613A, 5,021,556A, 5,075,099A, and 5,886,142A.

[0557] Representative chelating agents and their derivatives include, but are not limited to, AAZTA, BAT, CDTA, DTA, DTPA, CY-DTA, DTCBP, CTA, Cyclam, Cyclene, TETA, Sarcofazine, CPTA, TEAMA, Cyclene, DO3A, DO2A, TRITA, DATA, DFO, DATA(M), DATA(P), DATA(Ph), DATA(PPh), DEDPA, H4octapa, H2dedpa, H5decapa, H2azapa, and H2CHX. DEDPA, DFO-Chx-MAL, DFO-p-SCN, DFO-1AC, DFO-BAC, p-SCN-Bn-DFO, DFO-pPhe-NCS, DFO-HOPO, DFC, diphosphine, DOTA, DOTAGA, DOTA-MFCO, DOTAM-monoacid, nitro-DOTA, nitro-PA-DOTA, p-NCS-Bz- DOTA, PA-DOTA, DOTA-NCS, DOTA-NHS, CB-DO2A, PCTA, p-NH2-Bn-PCTA, p-SCN-Bn-PCTA, p-SCN-Bn-DOTA, DOTMA, NB-DOTA, H4NB-DOTA, H4TCE-DOTA, 3,4,3-(Li-1,2-HOPO), TREN(Me-3,2-HOPO), TCE-DOTA, DOTP, DOXP, p-NCS-DOTA, p-NCS-TRITA, TRITA, TETA, 3p-C-DEPA, 3p-C-DEPA-NCS, p-NH2-BN-OXO-DO3A, p-SCN-BN-TCMC, TCMC, 4-aminobutyl-DOTA, azido-mono-amide-DOTA, BCN-DOTA, butyne-DOTA, BCN-DOTA-GA, DOA3P, DO2a2p, DO2A(trans-H2do2a), DO3A, DO3A-thiol, DO3AtBu-N-(2-aminoethyl)ethaneamide, DO2AP, CB-DO2A, C3B-DO2A, HP-DO3A, DOT A-NHS-ester, maleimide-DOTA-GA, maleimide-mono-aminedo-DOTA, maleimide-DOTA, NH2-DOTA-GA, NH2-PEG4-DOTA-GA, GA, p-NH2-Bn-DOTA, p-NO2-Bn-DOTA, p-SCN-Bn-DOTA, p-SCN-Bz-DOTA, TA-DOTA, TA-DOTA-GA, OTTA, DOXP, TSC, DTC, DTCBP, PTSM, ATMS, H2ATSM, H2PTSM, Dp44mT, DpC, Bp44mT, QT, hybrid thiosemicarbazone-benzothiazole, thiosemicarbazone-styrylpyridinetetradentate ligand H2L, 2-4 , HBED, HBED-CC, dmHBED, dmEHPG, HBED-nn, SHBED, Br-Me2HBED, BPCA, HEHA, BF-HEHA, Deferiprone, THP, HYNIC Dorazinonicotinamide), NHS-HYNIC, HYNIC-Kp-DPPB, HYNIC-Ko-DPPB, (HYNIC)(Tricine)2, (HYNIC)(EDDA)Cl, p-EDDHA, AIM, AIM A, IAM B, MAMA, MAMA-DGal, MAMA-MGal, MAMA-DA, MAMA-HAD, Macropa, Macropaquin, Macroquin-SO3, N x S 4-x、N2S2、N3S、N4、MAG3B、NOTE、NODAGA、SCN-Bz-NOTE-R、NOT-P(NOTMP)、NOTAM、p-N CS-NOTE, TACN, TACN-TM, NETA, NETA-モアン, p-SCN-PhPr-NE3TA, C-NE3TA-NCS, C- NETA-NCS、3p-C-NETA、NODASE、NOPO、NODA、NO2A、 N-link-NODA, C-NOTA, BCNOT-link, ring-link-linkド-NOTE, NO2A-アジド, NO2A-Butyne, NO2AP, NO3AP, N-NOTE, Oxo-DO3A, p-NH2-Bn-NOTE, p-NH2-Bn-oxo-D O3A, p-NO2-Bn-Cyclen, p-SCN-Bn-NOTE, p-SCN-Bn-oxo-DO3A, TRAP, PAPER, BF-PAPER, Pycup, Pycup2A. pycup1A1Bn, pycup2Bn, SarAr-R, Diamsar, AmBaSar-R, siamSar, Sar, Tachpyr, tachpyr-(6-Me) TAM A、TAM B, TAME, TAME-Hex, THP-Ph-NCS, THP-NCS, THP-TATE, NTP, H3THP, THPN, CB-T E2A、PCB-TE1A1P、TETA-NHS、CPTA、CPTA-NHS、CB-TE1K1P、CB-TE2A、TE2A、H2C B-TE2A、TE2P、CB-TE2P、MM-TE2A、DM-TE2A、2C-TETA、6C-TETA、BAT、BAT-6、NH S-BAT, SSBAT, SCN-CHX-A-DTPA-P, SCN-TETA, TMT-protein, p-BZ-HTCPP.

[0558] HYNIC, DTPA, EDTA, DOTA, TETA, and bisaminobisthiol (BAT) based chelating agents disclosed in U.S. Patent No. 5,720,934; desferrioxamine (DFO) disclosed in Doulias et al., Free Radic Biol Med, 2003, Vol. 35:719; tetrapyridine and N3S, N2S2, and N4 chelating agents such as those disclosed in U.S. Patents No. 5,367,080A, 5,364,613A, 5,021,556A, 5,075,099A, and 5,886,142A; all references are incorporated herein by reference in their entirety; 6-amino-6-methylperhydro-1,4-diazepine-N,N',N'',N'''-tetraacetic acid (AAZTA) is a compound of Pfister et al. (Pfister et al., EJNMI Deferiprone, 1,2-dimethyl-3,4-hydroxypyridinone, and hexadentatetris(3,4-hydroxypyridinone)THP are disclosed in Res, 2015, Vol. 5:74; monoamine-monamidodithiol (MAMA)-based chelating agents are disclosed in Demoin et al. (Demoin et al., Nucl Med Biol, 2016, Vol. 43:802); MACROPA and its analogues are disclosed in Thiele et al. (Thiele et al., Angew 1,4,7,10,13,12-Hexaazacyclohexadecane-N,N',N'',N''',N'''',N'''''-Hexaacetic acid (HEHA) and its PEPA analogues are disclosed in Price et al. (Price et al., Chem Soc Rev, 2014, Vol. 43, p. 260), and Pycup and its analogues are disclosed in Boros et al. (Boros et al., Mol Disclosed in Pharm, 2014, Vol. 11: p. 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-tetraazacyclododecane-1-yl]pentan-2-yl)-amino]acetic acid (3p-C-DEPA), CB-TE2A, TE2A, TE1A1P, Diam sar, 1-N-(4-aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]-eicosane-1,8-diamine (SarAr), NETA, N,N0,N00,tris(2-mercaptoethyl)-1,4,7-triazazcyclononane (TACN-TM), {4-[2-(bis-carboxymethyl-amino)-ethyl]-7-carboxymethyl-[1,4,7]triazonan-1-yl}acetic acid (NETA), diethylenetriaminepentaacetic acid (DTP), 3-({4,7-bis-[(2-carboxy-ethyl)-hydroxy-phosphinoyl Lumethyl]-[1,4,7]triazonan-1-ylmethyl}-hydroxyphosphinoyl)-propionic acid (TRAP), NOPO, H4octapa, SHBED, BPCA, 3,6,9,15-tetraazabicyclo[9.3.1]-pentadeca-1(15), 11,13-triene-3,6,9-triacetic acid (PCTA), and 1,4,7,10,13-pentazacyclopentadecane-N,N',N'',N''',N''''-pentaacetic acid (PEPA) are disclosed in Price and Orvig (Price et al., Chem Soc Rev, 2014, vol. 43: p. 260), and 1-hydroxy-2-pyridone ligand (HOPO) is disclosed in Allott et al. (Allott et al., Chem [4-carboxymethyl-6-(carboxymethyl-methyl-amino)-6-methyl-[1,4]diazepam-1-yl]acetic acid (DATA) is disclosed in Commun (Camb), 2017, Vol. 53: 8529; [4-carboxymethyl-6-(carboxymethyl-methyl-amino)-6-methyl-[1,4]diazepam-1-yl]acetic acid (DATA) is disclosed in Tornesello et al. (Tornesello et al., Molecules, 2017, Vol. 22: 1282); tetrakis(aminomethyl)methane (TAM) and its analogues are disclosed in McAuley 1988 (McAuley et al., Canadian Journal of Chemistry, 1989, Vol. 67: 1657); and hexadentate tris(3,4-hydroxypyridinone) (THP) and its analogues are disclosed in Ma et al. (Ma et al., Dalton Trans, 2015, Vol. 44: 4884).

[0559] Some of the diagnostic and / or therapeutic uses of the above chelating agents are described in the prior art. For example, 2-hydrazinonicotinamide (HYNIC) 99m Tc and 186,188 It is widely used in the presence of coligands for Re incorporation (Schwartz et al., Bioconjug Chem, 1991, Vol. 2: p. 333; Babich et al., J Nucl Med, 1993, Vol. 34: p. 1964; Babich et al., Nucl Med Biol, 1995, Vol. 22: p. 25); DTPA is, 111It is used in Octreoscan® for the complexation of In, and several modifications are described in the literature (Li et al., Nucl Med Biol, 2001, Vol. 28: p. 145; Brechbiel et al., Bioconjug Chem, 1991, Vol. 2: p. 187); DOTA-type chelating agents for radiotherapy applications have been reported by Tweedle et al. (US Patent No. 4,885,363); other polyazama macrocyclic compounds for complexing trivalent isotope metals have been reported by Eisenwiener et al. (Eisenwiener et al., Bioconjug Chem, 2002, Vol. 13: p. 530); and 99m N4 chelators, such as Tc-N4 chelators, are used for peptide labeling in the case of minigastrins targeting the CCK-2 receptor (Nock et al., J Nucl Med, 2005, vol. 46: 1727).

[0560] In one embodiment, the metal chelating agent is not limited to DOTA, DOTAGA, NOTA, NODAGA, NODA-MPAA, HBED, TETA, CB-TE2A, DTPA, DFO, Macropa, HOPO, TRAP, THP, DATA, NOTP, sarcofazine, FSC, NETA, H4octapa, Pycup, N x S 4-x (N4, N2S2, N3S), Hynic, 99m Selected from the group including Tc(CO)3-chelating agents and their analogues, DOTA stands for 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid. DOTAGA stands for 1,4,7,10-tetraazacyclodosecane,1-(glutaric acid)-4,7,10-triacetic acid. NOTA stands for 1,4,7-triazacyclononane triacetic acid. NODAGA represents 1,4,7-triazacyclononane-N-glutaric acid-N',N''-diacetic acid, NODA-MPAA represents 1,4,7-triazacyclononane-1,4-diacetate-methylphenylacetic acid, HBED stands for bis(2-hydroxybenzyl)ethylenediaminediacetic acid. TETA stands for 1,4,8,11-tetraazacyclododecane-1,4,8,11-tetraacetic acid. CB-TE2A represents 4,11-bis-(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]-hexadecane, DTPA stands for diethylenetriaminepentaacetic acid. DFO represents the desferral or desferrioxamine type group of the chelating agent, and a non-restrictive example of the chemical name is N-[5-({3-[5-(acetyl-hydroxy-amino)-pentylcarbamoyl]-propionyl}-hydroxy-amino)-pentyl]-N'-(5-amino-pentyl)-N'-hydroxy-succinamide.

[0561] Macropa represents N,N'-bis[(6-carboxy-2-pyridyl)methyl]-4,13-diaza-18-crown, HOPO represents the octadentate hydroxypyridinone type group of the chelating agent, and a non-restrictive example structure is shown below.

[0562] TRAP represents 3-({4,7-bis-[(2-carboxy-ethyl)-hydroxyphosphinoylmethyl]-[1,4,7]triazonan-1-ylmethyl}hydroxyphosphinoyl)-propionic acid, THP stands for hexadentate tris(3,4-hydroxypyridinone), DATA represents [4-carboxymethyl-6-(carboxymethyl-methyl-amino)-6-methyl-[1,4]diazepan-1-yl]acetic acid, NOTP stands for 1,4,7-trizacyclononane-N,N',N''-tris(methylenephosphonic acid) acid, Sarcofazine represents 3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosan, FSC stands for 3,15,27-triamino-7,19,31-trihydroxy-10,22,34-trimethyl-1,13,25-trioxa-7,19,31-triaza-cyclohexatriaconta-9,21,33-triene-2,8,14,20,26,32-hexane, NETA represents {4-[2-(bis-carboxymethyl-amino)-ethyl]-7-carboxymethyl-[1,4,7]triazonan-1-yl}acetic acid, H4octap represents N,N'-(6-carboxy-2-pyridylmethyl)-N,N'-diacetic acid-1,2-diaminoethane, Pycup represents 1,8-(2,6-pyridinedimethylene)-1,4,8,11-tetraazacyclotetradecane, N x S 4-x (N4, N2S2, N3S) represents a group of tetradentate chelating agents having an N atom (basic amine or non-basic amide) and a thiol, which act as donors to stabilize Tc complexes, particularly Tc(V)-oxo complexes. The structure of MAG3, one representative non-limiting example, is shown below.

[0563] MAG3 represents {2-[2-(3-mercaptopropionylamino)-acetylamino]-acetylamino}acetic acid, HYNIC stands for 6-hydrazino-nicotinic acid, 99m Tc(CO)3-chelating agents represent bi or tridendate chelating agents that can form stable complexes with technetium tricarbonyl fragments. Their chemical structures are as follows:

[0564] [ka]

[0565] [ka]

[0566] In preferred embodiments, the metal chelating agent is selected from the group consisting of DOTA, DOTAGA, NOTA, NODAGA, NODA-MPAA, HBED, CB-TE2A, DFO, THP, N4, and their analogues.

[0567] In a more preferred embodiment, the metal chelating agent is selected from the group consisting of DOTA, DOTAGA, NOTA, N4Ac, and NODAGA, as well as their analogues. Those skilled in the art will recognize that chelating agents can be used in principle regardless of whether the compounds of the present invention are used or appropriate for diagnostic or therapeutic purposes. Such principles are outlined, in particular, in International Publication No. 2009 / 109332A1.

[0568] Furthermore, those skilled in the art will know that, unless otherwise stated, the presence of a chelating agent in the compounds of the present invention means that the chelating agent is an arbitrary metal complex partner, i.e., in principle, the chelating agent... It is recognized that this includes the possibility of complexing with any metal that can be complexed. The chelating agents explicitly described in the compounds of the present invention or the general term chelating agents related to the compounds of the present invention refer to chelating agents that are not thus complexed, or chelating agents to which any metal complex partner is bound, and the metal complex partner is any radioactive or non-radioactive metal complex partner. Preferably, the metal chelating agent complex, i.e., the chelating agent to which the metal complex partner is bound, is a stable metal chelating agent complex.

[0569] Non-radioactive metal chelating complexes have several applications, for example, for evaluating properties such as stability or activity that are difficult to determine in other respects. In one aspect, cold variants of radioactive versions of metal complex partners (e.g., non-radioactive gallium, lutetium, or indium complexes described in the examples) can act as substitutes for radioactive compounds. Furthermore, they are valuable tools for identifying metabolites in vitro or in vivo, as well as for evaluating the toxic properties of the compounds of the present invention. In addition, metal chelating complexes can be used in binding assays that utilize the fluorescence properties of several metal complexes having different ligands (e.g., europium salts).

[0570] Chelating agents can be synthesized or commercially available using a wide variety of (possibly already activated) groups for conjugation to peptides or amino acids. Direct conjugation of each compound of the present invention to amino nitrogen with a chelating agent is fully possible for chelating agents selected from the group consisting of DOTA, DOTAGA, NOTA, NODAGA, NODA-MPAA, HBED, TETA, CB-TE2A, DTPA, DFO, DATA, sarcofazine, N4, MAG3, and Hynic, preferably DOTA, DOTAGA, NOTA, NODAGA, NODA-MPAA, CB-TE2A, and N4. In this regard, the preferred linkage is an amide linkage.

[0571] Functional groups in chelating agents, which are ideal precursors for the 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, for example, NHS esters, pentafluorophenol esters, HOBt esters and HOAt esters, and isothiocyanates.

[0572] Functional groups in chelating agents, which are ideal precursors for the direct conjugation of chelating agent peptides to the carboxyl group, are known to those skilled in the art and include, but are not limited to, alkylamino and arylamino nitrogen groups. Each chelating agent reagent is for several commercially available chelating agents, e.g., for DOTAs having either alkylamino or arylamino nitrogen.

[0573] It will be recognized by those skilled in the art that the radionuclides to be bound to or attached to the compounds of the present invention are selected in consideration of the disease to be treated and / or diagnosed, and / or the specific characteristics of the population and group of patients to be treated and / or diagnosed, respectively.

[0574] In embodiments of this invention, radioactive nuclides are also called radionuclides. Radioactive decay is the process by which the nucleus of an unstable atom loses energy by emitting ionizing particles (ionizing radiation). There are various types of radioactive decay. Decay, or energy loss, occurs when an atom with one type of nucleus, called a parent radioactive nuclide, is transformed into an atom with a different state of nucleus, or into a different nucleus containing different numbers of protons and neutrons. All of these products are called daughter nuclides. In some decays, the parent and daughter are different chemical elements, and therefore the decay process results in nuclear transmutation (the creation of atoms of new elements). For example, radioactive decay can be alpha decay, beta decay, and gamma decay. Alpha decay occurs when a nucleus emits an alpha particle (helium nucleus). This is the most common process of emitting a nucleon, but in rare types of decay, the nucleus emits a proton or a specific nucleus of another element (in a process called cluster decay). Beta decay is a process in which a proton is transformed into a neutron or vice versa, in which the nucleus transforms into an electron (β - -decay) or positron (β) +This occurs when a nucleus undergoes a decay (gamma decay) and emits a type of neutrino. In contrast, there are radioactive decay processes that do not produce mutations. The energy of an excited nucleus is either emitted as gamma rays in gamma decay, or used to emit orbital electrons through interaction with the excited nucleus in a process called internal conversion, or used to absorb inner atomic electrons from electron shells, thereby causing the change of nuclear protons to neutrons to trigger the emission of electron neutrinos in a process called electron capture (EC), or to be emitted without changing the number of protons and neutrons in a process called isomer transition (IT). Another form of radioactive decay, spontaneous fission (SF), is found only in very heavy chemical elements and results in the spontaneous disintegration of smaller nuclei and a few isolated nuclear particles.

[0575] In a preferred embodiment of the present invention, a radionuclide can be used to label the compound of the present invention. In embodiments of the present invention, the radionuclide is suitable for complex formation with the chelating agent, resulting in a radionuclide chelate complex.

[0576] In further embodiments, one or more atoms of the compounds of the present invention are a non-natural isotopic composition, preferably these atoms are radionuclides, more preferably radionuclides of carbon, oxygen, nitrogen, sulfur, phosphorus, and halogens: these radioactive atoms are typically part of an amino acid, optionally a halogen-containing amino acid and / or component, optionally a halogenated component of each of the compounds of the present invention.

[0577] In a preferred embodiment of the present invention, the radionuclide has a half-life that enables diagnostic and / or therapeutic medical use. Specifically, the half-life is between 1 minute and 100 days. In preferred embodiments of the present invention, the radionuclides have decay energies that enable diagnostic and / or therapeutic medical use. Specifically, for γ-emitting isotopes, the decay energy is 0.004 to 10 MeV, preferably 0.05 to 4 MeV, for diagnostic use. For positron-emitting isotopes, the decay energy is 0.6 to 13.2 MeV, preferably 1 to 6 MeV, for diagnostic use. For particle-emitting isotopes, the decay energy is 0.039 to 10 MeV, preferably 0.4 to 6.5 MeV, for therapeutic use.

[0578] In a preferred embodiment of the present invention, the radionuclide is industrially manufactured for medical use. Specifically, the radionuclide is available in GMP quality. In preferred embodiments of the present invention, the daughter nuclide(s) after the radioactive decay of a radionuclide are suitable for diagnostic and / or therapeutic medical use. Furthermore, the daughter nuclide is stable or decays further in a manner that does not interfere with, or even support, diagnostic and / or therapeutic medical use. Representative radionuclides that may be used in connection with the present invention are summarized in Table 7.

[0579] [Table 7-1]

[0580] [Table 7-2]

[0581] [Table 7-3]

[0582] [Table 7-4]

[0583] [Table 7-5]

[0584] Table 7-6

[0585] Table 7-7

[0586] Table 7-8

[0587] Table 7-9

[0588] Table 7-10

[0589] Table 7-11

[0590] Table 7-12

[0591] Table 7-13

[0592] Table 7-14

[0593] Table 7-15

[0594] Table 7-16

[0595] Table 7-17

[0596] Table 7-18

[0597] Table 7-19

[0598] Table 7-20

[0599] Table 7-21

[0600] Table 7-22

[0601] Table 7-23

[0602] Table 7-24

[0603] Table 7-25

[0604] [Table 7-26]

[0605] [Table 7-27]

[0606] [Table 7-28]

[0607] [Table 7-29]

[0608] [Table 7-30]

[0609] [Table 7-31]

[0610] [Table 7-32]

[0611] [Table 7-33]

[0612] [Table 7-34]

[0613] In embodiments of the present invention, radionuclides are used for diagnostic purposes. Preferably, radioisotopes are, but are not limited to, 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 Selected from the group including I. More preferably, the radionuclide is 43 Sc, 44 Sc, 64 Cu, 67 Ga, 68 Ga, 86 Y, 89 Zr, 99m Tc, 111 In, 152 Tb, 155 Tb, 203 Pb, 18 F, 76 Br, 77 Br, 123 I, 124 I, 125 Selected from the group including I. More preferably, radionuclides are 64 Cu, 68 Ga, 89 Zr, 99m Tc, 111 In, 18 F, 123 I, and 12 4 Selected from the group including I. However, it will be recognized by those skilled in the art that the use of the above radionuclides is not limited to diagnostic purposes, but also includes their use in therapeutic and diagnostic therapies when conjugated with the compounds of the present invention.

[0614] In embodiments of the present invention, the radionuclide is used for treatment. Preferably, the radioisotope is 47 Sc,67 Cu, 89 Sr, 90 Y, 111 In, 153 Sm, 149 Tb, 161 Tb, 177 Lu, 186 Re, 188 Re, 212 Pb, 213 Bi, 223 Ra, 225 Ac, 226 Th, 227 Th, 131 I, 211 Selected from the group including At. More preferably, the radioactive isotope is 47 Sc, 67 Cu, 90 Y, 177 Lu, 188 Re, 212 Pb, 213 Bi, 225 Ac, 227 Th, 131 I, 211 Selected from the group including At. More preferably, the radionuclide is 90 Y, 177 Lu, 225 Ac, 227 Th, 131 I and 211 The radionuclides are selected from the group including At. However, it will be recognized by those skilled in the art that the use of the above radionuclides is not limited to therapeutic purposes, but also includes their use in diagnosis and diagnostic therapy when conjugated in the compounds of the present invention.

[0615] In one embodiment, the compound of the present invention exists as a pharmaceutically acceptable salt. The "pharmaceutically acceptable salts" of the compounds of the present invention are preferably acidic or basic salts that are generally considered in the art to be suitable for use in contact with human or animal tissue without excessive toxicity or carcinogenicity, preferably without irritation, allergic reactions, or other problems or complications. Such salts include mineral and organic acid salts of basic residues such as amines, as well as alkali or organic salts of acidic residues such as carboxylic acids. The compounds of the present invention can also form internal salts that are pharmaceutically acceptable salts.

[0616] Appropriate pharmaceutically acceptable salts include, but are not limited to, hydrochloric acid, phosphoric acid, bromate, 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, alkanic acid, e.g., acetic acid, HOOC-(CH2) n Examples include salts of acids such as -COOH (where 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 skilled in the art will recognize further pharmaceutically acceptable salts of the compounds provided herein. In general, pharmaceutically acceptable acid or base salts can be synthesized from parent compounds containing a basic or acidic moiety by any conventional chemical method. Briefly, such salts can be prepared by reacting the free acid or free base form of these compounds with a stoichiometric amount of a suitable base or acid in water or an organic solvent, or in a mixture of the two. Generally, the use of non-aqueous media such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile is preferred.

[0617] The "pharmaceutically acceptable solvate" of the compound of the present invention is preferably a solvate of the compound of the present invention formed by the association of one or more solvent molecules with one or more molecules of the compound of the present invention. Preferably, the solvent is one that is generally considered in the art to be suitable for use in contact with human or animal tissue without excessive toxicity or carcinogenicity, preferably without irritation, allergic reactions, or other problems or complications. Such solvents include organic solvents such as alcohols, ethers, esters, and amines.

[0618] The "hydrates" of the compounds of the present invention are formed by the association of one or more water molecules with one or more molecules of the compounds 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.

[0619] The compounds of the present invention have high binding affinity to FAP and high inhibitory activity against FAP. Due to this high binding affinity, the compounds of the present invention are effective, useful, and / or suitable as targeting agents and, when conjugated to another part, as targeting parts. Preferably in this specification, the targeting agent is a drug that interacts with the target molecule, which is FAP in this case. Accordingly, with respect to cells and tissues targeted by the compounds of the present invention, any cells and tissues expressing FAP can be targeted or made to target.

[0620] In one embodiment, the compound interacts with fibroblast-activating protein (FAP), preferably human FAP having the amino acid sequence of SEQ ID NO: 1 or a homologue thereof, wherein the homologue's amino acid sequence has FAP identity that is at least 85% of the amino acid sequence of SEQ ID NO: 1. In a preferred embodiment, the identity is 90%, preferably 95%, 96%, 97%, 98%, or 99%.

[0621] The identity between two nucleic acid molecules can be determined in a manner known to those skilled in the art. More specifically, a sequence comparison algorithm can be used to calculate the sequence homology percentage of a test sequence(s) to a reference sequence based on specified program parameters. The test sequence is preferably a sequence or protein or polypeptide that is said to be identical to, or to be tested for, whether it is identical to, and if so, to what extent it is identical to, a different protein or polypeptide, thereby also being called a reference sequence, preferably a wild-type protein or polypeptide, more preferably human FAP of SEQ ID NO: 1.

[0622] The optimal alignment of sequences for comparison can be determined, for example, by the local homology algorithm of Smith & Waterman (Smith et al., Advances in Applied Mathematics, 1981, Vol. 2: p. 482) and the Needleman algorithm. This can be done by the homology alignment algorithm of Wunsch (Needleman et al., J Mol Biol, 1970, Vol. 48: p. 443), by the similarity search of Pearson & Lipman (Pearson et al., Proc Natl Acad Sci USA, 1988, Vol. 85: p. 24444), by computerized implementation of these algorithms (GAP, BESTFIT, FASTA, and TFASTA from the Wisconsin Genetics software package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by visual inspection.

[0623] One example of a suitable algorithm for determining sequence identity percentage is the algorithm used in the Basic Local Alignment Search Tool (hereinafter referred to as "BLAST"). See, for example, Altschul et al., 1990 (Altschul et al., J Mol Biol, 1990, vol. 215: p. 403) and Altschul et al., 1997 (Altschul et al., Nucleic Acids Res, 1997, vol. 25: p. 3389). Software for performing BLAST analysis is publicly available through the National Center for Biotechnology Information (hereinafter referred to as "NCBI"). Software available from NCBI, for example, BLASTN (for nucleotide sequences) The default parameters used when determining sequence identity using BLASTP (for amino acid sequences) are described in McGinnis et al. (McGinnis et al., Nucleic Acids Res, 2004, Vol. 32:W20).

[0624] It is within the scope of the present invention that the compounds of the present invention may be used or intended for use in methods for treating diseases disclosed herein. Such methods preferably include the step of administering a therapeutically effective amount of the compounds of the present invention to a subject in need. Such methods may include, but are not limited to, curative or adjuvant cancer treatments. They may be used as palliative treatment when a cure is not possible and the purpose is local disease control or symptom relief, or as therapeutic treatment when the therapy has a survival benefit and may be curative.

[0625] The methods for treating diseases disclosed herein include treatment of tumors and cancers, and can be used as a first therapy, or as a second, third, fourth, or final therapy. Combining the compounds of the present invention with further therapeutic methods is also within the scope of the invention. It is well known to those skilled in the art that the exact intent of treatment, including curative, adjuvant, neoadjuvant, therapeutic, or palliative treatment, depends on the type, location, and stage of the tumor, as well as the patient's general health.

[0626] In embodiments of the present invention, the disease is an unspecified neoplasm, a benign neoplasm, a neoplasm of unknown benign or malignant nature, a malignant neoplasm, a metastatic neoplasm, a neoplasm of unknown primary or metastatic nature, a benign tumor cell, a tumor cell of unknown benign or malignant nature, a malignant tumor cell, a small cell malignant tumor, a giant cell malignant tumor, a spindle cell malignant tumor, an unspecified epithelial neoplasm, a benign epithelial tumor, an unspecified in situ cancer, an unspecified metastatic cancer, carcinomatosis, a benign epithelioma, a malignant epithelioma, an unspecified large cell carcinoma, an unspecified undifferentiated carcinoma, an unspecified dysplastic carcinoma, a pleomorphic carcinoma, a giant cell and spindle cell carcinoma, a giant cell carcinoma, a spindle cell carcinoma, a pseudosarcomatoid carcinoma, a pleomorphic cell carcinoma, a spheroid cell carcinoma, multiple small tumors, an unspecified small cell carcinoma, an oat cell carcinoma, a small cell carcinoma, a spindle cell type, a papillary and squamous cell neoplasm, an unspecified papilloma, in Situ papillary carcinoma, unspecified papillary carcinoma, wart-like papilloma, unspecified wart-like carcinoma, squamous cell papilloma, squamous cell carcinoma, inverted papilloma, unspecified papillomatosis, unspecified in situ squamous cell carcinoma, unspecified squamous cell carcinoma, unspecified metastatic squamous cell carcinoma, squamous cell carcinoma, unspecified keratinized type, large cell nonkeratinized squamous cell carcinoma, small cell nonkeratinized squamous cell carcinoma, spindle cell type squamous cell carcinoma, adenoid squamous cell carcinoma, suspected stromal invasion in Situ squamous cell carcinoma, minimally invasive squamous cell carcinoma, Keiler's red hyperplasia, Bowen's disease, lymphoepithelial carcinoma, basal cell neoplasm, basal cell tumor, unspecified basal cell carcinoma, multicentric basal cell carcinoma, focal scleroderma-type basal cell carcinoma, fibroepithelial basal cell carcinoma, basal squamous cell carcinoma, degenerative carcinoma, Yadazon-type intraepidermal epithelioma, follicular epithelioma, follicular septum, piloplasty, calcifying epithelioma, transitional cell papilloma and carcinoma, unspecified transitional cell papilloma, urothelial papilloma, in situ transitional cell carcinoma, unspecified transitional cell carcinoma, Schneiderian papilloma, inverted transitional cell papilloma, Schneiderian carcinoma, spindle cell transitional cell carcinoma, basal cell carcinoid, cloacal carcinoma, papillary transitional cell carcinoma, adenoma and adenocarcinoma, unspecified adenoma, unspecified bronchial adenoma, inSitu adenocarcinoma, unspecified adenocarcinoma, unspecified metastatic adenocarcinoma, scirrhous adenocarcinoma, plastic gastric fibrosis, superficial spreading adenocarcinoma, intestinal adenocarcinoma, diffuse adenocarcinoma, monomorphic adenoma, basal cell adenoma, islet cell adenoma, islet cell carcinoma, unspecified insulinoma, malignant insulinoma, unspecified glucagonoma, malignant glucagonoma, unspecified gastrinoma, malignant gastrinoma, mixed islet cell and exocrine adenocarcinoma, cholangioadenoma, cholangiocarcinoma, cholangiocystadenoma, cholangiocystadenocarcinoma, hepatocellular adenoma, unspecified hepatocellular carcinoma, benign hepatocellular cholangiomoma Mixed hepatocellular carcinoma and cholangiocarcinoma, cord-like adenoma, cord-like adenocarcinoma, embryonic adenoma, eccrine cutaneous cystic carcinoma, adenoid cystic carcinoma, cribriform carcinoma, unspecified adenomatous polyp, adenocarcinoma in adenomatous polyp, unspecified tubular adenoma, tubular adenocarcinoma, adenomatous polyposis of the colon, adenocarcinoma in adenomatous polyposis of the colon, multiple adenomatous polyps, unspecified solid tumor, simple carcinoma, unspecified carcinoid tumor, malignant carcinoid tumor, unspecified silver-affinity carcinoid tumor, malignant silver-affinity carcinoid tumor, unspecified non-silver-affinity carcinoid tumor Carcinoid tumors, malignant non-silver affinity carcinoid tumors, malignant mucinous carcinoid tumors, complex carcinoid tumors, pulmonary adenomatosis, bronchiolar-alveolar adenocarcinoma, hydatidiform adenoma, hydatidiform adenocarcinoma, unspecified papillary adenoma, unspecified papillary adenocarcinoma, unspecified chorioadenoma, adenocarcinoma in chorioadenoma, chorioadenocarcinoma, tubular chorioadenoma, pigmentaphobic adenoma, pigmentaphobic carcinoma, eosinophilic adenoma, eosinophilic carcinoma, eosinophilic-basophilic mixed adenoma, eosinophilic-basophilic mixed carcinoma, eosinophilic adenoma, eosinophilic adenocarcinoma, basophilic adenoma, basophilic carcinoma, clear cell adenoma, unspecified clear cell adenocarcinoma, adrenal gland-like tumors, renal cell carcinoma, clear cell adenofibrilloma, granular cell carcinoma, principal cell adenoma, Aqueous clear cell adenoma, aqueous clear cell adenocarcinoma, mixed cell adenoma, mixed cell adenocarcinoma, lipodenoma, vesicular adenoma, unspecified vesicular adenocarcinoma, well-differentiated vesicular adenocarcinoma, cord-like vesicular adenocarcinoma, small follicular adenoma, large follicular adenoma, papillary and follicular adenocarcinoma, non-encapsulated sclerosing carcinoma, multiple endocrine adenoma, juxtaglomerular tumor, unspecified adrenocortical adenoma, adrenocortical cell carcinoma, compact cell adrenocortical adenoma, severely pigmented adrenocortical adenoma, clear cell adrenocortical adenoma, zonal cell adrenocortical adenoma, mixed cell adrenocortical adenoma, unspecified endometrioid adenoma, endometrioid adenoma, borderline malignant tumor, endometrioid carcinoma, unspecified uterine Endometrial fibroma, borderline malignant tumor, malignant endometrial fibroma, cutaneous adnexal neoplasm, cutaneous adnexal adenoma, cutaneous adnexal carcinoma, sweat adenoma, unspecified sweat gland tumor, sweat gland carcinoma, apocrine adenoma, apocrine gland carcinoma, eccrine apical sweat adenoma, eccrine spiral adenoma, sweat gland cyst, papillary sweat adenoma, papillary sweat adenoma, unspecified syringoma, sebaceous adenoma, sebaceous gland carcinoma, ceruminous adenoma, ceruminous gland carcinoma, mucosal epidermal neoplasm, mucosal epidermal tumor, mucosal epidermal carcinoma, cystic, mucinous, and serous neoplasms, unspecified cystadenoma, unspecified cystadenocarcinoma, unspecified serous cystadenoma, serous cystadenoma, borderline malignant tumor, unspecified serous cystadenocarcinoma, unspecified papillary cystadenoma, papillary cystadenomatous borderline malignant tumor, unspecified papillary cystadenocarcinoma, unspecified papillary serous cystadenoma, papillary serous cystadenoma borderline malignant tumor, papillary serous cystadenocarcinoma, unspecified serous superficial papilloma, serous superficial papilloma borderline malignant tumor, Serous superficial papillary carcinoma, unspecified mucinous cystadenoma, mucinous cystadenoma borderline malignant tumor, unspecified mucinous cystadenocarcinoma, unspecified papillary mucinous cystadenoma, papillary mucinous cystadenoma borderline malignant tumor, papillary mucinous cystadenocarcinoma, mucinous adenoma, mucinous adenocarcinoma, peritoneal pseudomyxoma, mucin-producing adenocarcinoma, signet ring cell carcinoma,Metastatic signet ring cell carcinoma, tubular, lobular, and medullary neoplasms, unspecified intraductal carcinoma in situ, invasive ductal carcinoma, comedone carcinoma, unspecified non-invasive comedone carcinoma in situ, juvenile thoracic cancer, intraductal papilloma, uninvasive intraductal papillary adenocarcinoma, intracystic papilloid adenoma, uninvasive intracystic carcinoma in situ, unspecified intraductal papilloma, subareolar ductal papilloma, unspecified medullary carcinoma, amyloid-stromal medullary carcinoma, lymphocyte-stromal medullary carcinoma, in lobular carcinoma in situ, lobular carcinoma not otherwise specified, invasive ductal carcinoma, inflammatory carcinoma, Paget's disease of the breast, Paget's disease and invasive ductal carcinoma, extramammary Paget's disease, acinar cell neoplasm, acinar cell adenoma, acinar cell tumor, acinar cell carcinoma, complex epithelial neoplasm, glandular Squamous cell carcinoma, glandular lymphoma, squamous metaplastic adenocarcinoma, chondrogenic and osseous metaplastic adenocarcinoma, spindle cell metaplastic adenocarcinoma, apocrine metaplastic adenocarcinoma, benign thymoma, malignant thymoma, specific gonadal neoplasm, sex cord-stromal tumor, theca cell carcinoma unspecified, theca cell carcinoma, unspecified type Luteal malformation, unspecified granulosa cell tumor, malignant granulosa cell tumor, granulosa cell-follicular cell tumor, benign male germ cell tumor, unspecified male germ cell tumor, malignant male germ cell tumor, Sertoli-Leydig cell tumor, ovarian male germ cell tumor, unspecified tubular male germ cell tumor, Sertoli cell carcinoma, lipid-storing tubular male germ cell tumor, benign Leydig cell tumor, unspecified Leydig cell tumor, malignant Leydig cell tumor, hilar cell tumor, ovarian lipid cell tumor, adrenal quiescent tumor, paraganglioma and glomus tumor, unspecified para Gangliomas, malignant paragangliomas, sympathetic paragangliomas, parasympathetic paragangliomas, jugular vein body tumors, aortic body tumors, carotid bulb tumors, extraadrenal paragangliomas of unspecified type, malignant extraadrenal paragangliomas, pheochromocytomas of unspecified type, malignant pheochromocytomas, angiobulbar angiosarcomas, glomus tumors, glomus hemangiomas, nevi and melanomas, pigmented nevi of unspecified type, malignant melanoma of unspecified type, nodular melanoma, balloon cell nevi, balloon cell melanoma, halo nevi, fibrous papules of the nose, neuronal nevi, giant cell nevi, non-pigmented nevi, Melanin-deficient melanoma, junctional nevus, malignant melanoma in junctional nevus, unspecified precancerous melanosis, malignant melanoma in precancerous melanosis, Hutchinson's melanosis, malignant melanoma in Hutchinson's melanosis, superficial spreading melanoma, intradermal nevus, compound nevus, giant pigmented nevus, malignant melanoma in giant pigmented nevus, epithelioid nevus and spindle cell nevus, epithelioid melanoma, unspecified spindle cell melanoma, spindle cell melanoma type a, spindle cell melanoma type b, mixed epithelioid and spindle cell melanoma,Unspecified blue nevus, malignant, Blue nevus, cell proliferation blue nevus, unspecified soft tissue tumors and sarcomas, benign soft tissue tumors, unspecified sarcomas, unspecified sarcomas, spindle cell sarcoma, giant cell sarcoma, small cell sarcoma, epithelioid cell sarcoma, fibromatoid neoplasms, unspecified fibroma, unspecified fibrosarcoma, myxofibroma, fibromyxosarcoma, periosteal fibroma, periosteal fibrosarcoma, fascial fibroma, fascial fibrosarcoma, infantile fibrosarcoma, elastic fibroma, invasive fibromatosis, abdominal fibromatosis, tendonoid fibroma, unspecified fibrous histiocytoma, atypical fibrous histiocytoma, malignant fibrous histiocytoma, unspecified fibroxanthoma, atypical fibroxanthoma, malignant fibroxanthoma , unspecified dermatofibroma, dermatofibroma protuberans, unspecified dermatofibrosarcoma, myxomatous neoplasm, unspecified myxoma, myxosarcoma, lipomatous neoplasm, unspecified lipoma, unspecified liposarcoma, fibrolipoma, well-differentiated liposarcoma, fibromyxolipoma, myxoid liposarcoma, round cell liposarcoma, pleomorphic liposarcoma, mixed liposarcoma, intramuscular lipoma, spindle cell lipoma, angiomyolipoma, angiomyoliposarcoma, unspecified angiolipoma, invasive angiolipoma, myelolipoma, hibernating adenoma, lipoblastomatosis, myomatous neoplasm, unspecified leiomyoma, intravascular leiomyomatosis, unspecified leiomyosarcoma, epithelioid smooth muscle Tumor, epithelioid leiomyoma, cellular leiomyoma, deformed leiomyoma, angiomyoma, angiosarcoma, myoma, myosarcoma, unspecified rhabdomyomyoma, unspecified rhabdomyomyoma, pleomorphic rhabdomyomyoma, mixed rhabdomyomyoma, fetal rhabdomyomyoma, adult rhabdomyomyoma, fetal rhabdomyomyoma, alveolar rhabdomyomyoma, complex mixed and stromal neoplasms, endometrial stromal sarcoma, endolymphoid stromal endometriosis, adenomyoma, pleomorphic adenoma, unspecified malignant mixed tumor, Müllerian mixed tumor, mesodermal mixed tumor, mesodermal nephromas, unspecified nephroblastoma, epithelial nephroblastoma, mesenchymal nephroblastoma, hepatoblastoma, unspecified carcinosarcoma, fetal carcinosarcoma, muscle Epithelioma, benign mesenchymal tumor, unspecified mesenchymal tumor, malignant mesenchymal tumor, embryonal sarcoma, fibroepithelial neoplasm, unspecified Brenner tumor, borderline malignant Brenner tumor, malignant Brenner tumor, unspecified fibroadenoma, unspecified intraductal fibroadenoma, periductal fibroadenoma, unspecified adenofibrilloma, serous adenofibrilloma, myxoid adenofibrilloma, cellular intraductal fibroadenoma, unspecified phyllodes sarcoma, malignant phyllodes sarcoma, juvenile fibroadenoma, synovial neoplasm, benign synovial tumor, unspecified synovial sarcoma, spindle cell type synovial sarcoma, epithelioid cell type synovial sarcoma, biphasic synovial sarcoma, clear cell sarcoma of tendons and aponeuroses, mesothelial neoplasm, benign mesothelioma,Malignant mesothelioma, benign fibrous mesothelioma, malignant fibrous mesothelioma, benign epithelioid mesothelioma, malignant epithelioid mesothelioma, benign biphasic mesothelioma, malignant biphasic mesothelioma, unspecified adenoid tumor, germ cell neoplasm, undifferentiated germ cell tumor, unspecified seminomas, undifferentiated seminomas, spermatogenic seminomas, germ cell tumor, unspecified embryonic cancer, endodermal sinus tumor, polyembryo tumor, gonadal blastoma, benign teratoma, unspecified teratoma, unspecified malignant teratoma, teratogenic carcinoma, undifferentiated malignant teratoma, intermediate malignant teratoma, dermoid cyst, malignant transforming dermoid cyst, unspecified ovarian goiter, malignant ovarian goiter, goiter carcinoid, trophoblast neoplasm , unspecified hydatidiform mole, invasive hydatidiform mole, choriocarcinoma, choriocarcinoma with teratoma, malignant trophoblast teratoma, mesonephroma, benign mesonephroma, mesonephroma, malignant mesonephroma, endometrioma, hemangiotumor, unspecified hemangioma, hemangiosarcoma, cavernous hemangioma, venous hemangioma, vine-like hemangioma, Kupffer cell sarcoma, benign hemangioendothelioma, unspecified hemangioendothelioma, malignant hemangioendothelioma, capillary hemangioma, intramuscular hemangioma, Kaposi's sarcoma, angiokeratomas, warty angiokeratomas, benign periangiocarcinoma, unspecified periangiocarcinoma, malignant periangiocarcinoma, unspecified hemangiofibroma, hemangioblastoma, lymphangiotumor, unspecified lymphangiomas, lymph Tongosarcoma, capillary lymphangioma, cavernous lymphangioma, cystic lymphangioma, lymphangiomyomatosis, lymphangiomyomatosis, angiolymphangioma, osteoma and osteosarcoma, unspecified osteoma, unspecified osteosarcoma, chondroblastic osteosarcoma, fibroblastic osteosarcoma, pyogenic osteosarcoma, osteosarcoma in Paget's disease of bone, paraosteal osteosarcoma, unspecified osteoid osteoma, osteoblastoma, chondroplastic neoplasm, osteochondroma, unspecified osteochondromatosis, unspecified chondroma, unspecified chondroma, unspecified chondrosarcoma, paraosteal chondroma, paraosteal chondrosarcoma, unspecified chondroblastoma, malignant chondroblastoma, mesenchymal chondrosarcoma, cartilage myxoplasm Giant cell tumor, unspecified giant cell tumor of bone, malignant giant cell tumor of bone, unspecified giant cell tumor of soft tissue, malignant giant cell tumor of soft tissue, mixed bone tumor, Ewing's sarcoma, long bone adamantinoma, ossifying fibroma, odontogenic tumor, benign odontogenic tumor, unspecified odontogenic tumor, malignant odontogenic tumor, dentinoma, unspecified cementoma, benign cementoblastoma, cementoplastic fibroma, giant cementoma, unspecified odontoma, aggregate odontoma, complex odontoma, ameloblastoma, epiameloblastoma, adenoid odontogenic tumor, calcifying odontogenic cyst, unspecified ameloblastoma, malignant ameloblastoma,teeth, Dental ameloblastoma, squamous odontogenic tumor, odontogenic myxoma, unspecified odontogenic fibroma, ameloblastoma, ameloblastoma, odontogenic calcifying epithelioma, mixed tumor, craniopharyngioma, pinealoma, pineal cell tumor, pineoblastoma, melanotic neuroectodermal tumor, chordoma, glioma, malignant glioma, cerebral gliomatosis, mixed glioma, subependymal glioma, subependymal giant cell astrocytoma, unspecified choroid plexus papilloma, malignant choroid plexus papilloma, unspecified ependymoma, undifferentiated ependymoma, papillary ependymoma, myxopapillary ependymoma, unspecified astrocytoma, undifferentiated astrocytoma, protoplasmic astrocytoma, Hypertrophic astrocytoma, fibrous astrocytoma, pilocytic astrocytoma, unspecified cavernous blastoma, polar cavernous blastoma, astrocytoma, unspecified glioblastoma, giant cell glioblastoma, glioblastoma with sarcomatoid elements, primitive polar cavernous blastoma, unspecified oligodendroglioma, undifferentiated oligodendroglioma, oligodendroglioma, unspecified medulloblastoma, fibroplastic medulloblastoma, medullomyobioma, unspecified cerebellar sarcoma, teratocytoma, pseudoepitheliomatous neoplasm, gangliocytoma, ganglioblastoma, ganglioneuromatosis, unspecified neuroblastoma, unspecified medullary epithelioma, teratoid medullary epithelioma, unspecified neuroblastoma Cavernous neuroblastoma, ganglioglioma, neurocytoma, Pacinian tumor, unspecified retinoblastoma, differentiated retinoblastoma, undifferentiated retinoblastoma, olfactory neurotumor, sensory neurocytoma, nasal sacral neuroblastoma, olfactory neuroepithelioma, meningioma, unspecified meningioma, unspecified meningiomatosis, malignant meningioma, meningeal meningioma, fibrous meningioma, miliary meningioma, hemangioma, hemangioblastic meningioma, perivascular meningioma, transitional meningioma, papillary meningioma, meningosarcoma, nerve sheath tumor, unspecified neurofibroma, unspecified neurofibromatosis, neurofibrosarcoma, melaninous neurofibroma, plexiform neurofibroma, unspecified Brute-type schwannoma, schwannoma syndrome, malignant schwannoma, unspecified neuroma, granuloma and alveolar soft part sarcoma, unspecified granuloma, malignant granuloma, alveolar soft part sarcoma, unspecified or diffuse lymphoma, benign lymphomatoid tumor, unspecified malignant lymphoma, non-Hodgkin type malignant lymphoma, unspecified undifferentiated malignant lymphoma, stem cell type malignant lymphoma, unspecified circumflex cell type malignant lymphoma, unspecified lymphosarcoma, lymphoplasmacytic type malignant lymphoma, immunoblastic type malignant lymphoma, unspecified mixed lymphocyte-histiocytic malignant lymphoma, centroblastic centrocellular diffuse malignant lymphoma,Unspecified follicular central cell lymphoma, unspecified well-differentiated lymphocytic lymphoma, unspecified moderately differentiated lymphocytic lymphoma, unspecified schizotypal central cell lymphoma, unspecified poorly differentiated lymphocytic lymphoma, prolymphocytic lymphosarcoma, unspecified centroblastic lymphoma, unspecified unschizotypal follicular central cell lymphoma, reticulum sarcoma, unspecified reticulum sarcoma, pleomorphic cell reticulum sarcoma, nodular reticulum sarcoma, Hodgkin's disease, unspecified Hodgkin's disease, lymphocyte-dominant Hodgkin's disease, mixed cell type Hodgkin's disease, unspecified lymphocyte Depletion-type Hodgkin's disease, lymphocyte-depletion-type diffuse fibromatosis-type Hodgkin's disease, lymphocyte-depletion-type reticular Hodgkin's disease, unspecified nodular sclerosis-type Hodgkin's disease, cytological nodular sclerosis-type Hodgkin's disease, Hodgkin's granuloma, Hodgkin's granuloma, Hodgkin's sarcoma, nodular lymphoma or unspecified follicular nodular lymphoma, nodular mixed lymphocyte-histiocytic lymphoma, centroblastic centrocyte follicular lymphoma, nodular well-differentiated lymphocytic lymphoma, nodular moderately differentiated lymphocytic lymphoma, follicular truncated follicular centrocyte lymphoma, nodular poorly differentiated lymphocytic lymphoma, Follicular non-segmental follicular centrocellular lymphoma, centroblastic lymphoma, mycosis fungoides, mycosis fungoides, Sézary's disease, mixed reticuloendoplasma, microglioma, malignant histiocytic proliferative disorder, histiocytic medullary reticular disease, Lether-Sibe disease, plasma cell tumor, plasma cell myeloma, benign plasma cell tumor, unspecified plasma cell tumor, malignant plasma cell tumor, mast cell tumor, unspecified mast cell tumor, mast cell sarcoma, malignant mastocytosis, Burkitt's tumor, Burkitt's tumor, leukemia group, unspecified leukemia group, unspecified leukemia, unspecified acute leukemia, unspecified subacute leukemia, unspecified chronic leukemia , unspecified non-leukemia, combined leukemia group, combined leukemia, lymphocytic leukemia group, unspecified lymphocytic leukemia, acute lymphoblastic leukemia, subacute lymphocytic leukemia, chronic lymphocytic leukemia, nonleukemic lymphocytic leukemia, prolymphocytic leukemia, plasma cell leukemia group, plasma cell leukemia, erythroleukemia group, erythroleukemia, acute erythremia, chronic erythremia, lymphosarcomacytic leukemia group, lymphosarcomacytic leukemia, myeloid leukemia group, unspecified myeloid leukemia, acute myeloid leukemia, subacute myeloid leukemia, chronic myeloid leukemia, nonleukemic myeloid leukemia, neutrophilic leukemia, acute promyelocytic leukemia,Basophilic leukemia, The group is selected from the following categories: basophilic leukemia, eosinophilic leukemia, eosinophilic leukemia, monocytic leukemia, unspecified monocytic leukemia, acute monocytic leukemia, subacute monocytic leukemia, chronic monocytic leukemia, nonleukemic monocytic leukemia, mixed leukemia, mast cell leukemia, megakaryocytic leukemia, megakaryocytic myelopathy, myeloid sarcoma, hairy cell leukemia, mixed myeloproliferative lymphoproliferative disorder, polycythemia vera, acute panmyelopathy, chronic myeloproliferative disorder, myelosclerosis complicated with myeloid metaplasia, idiopathic thrombocythemia, and chronic lymphoproliferative disorder.

[0627] In embodiments of the present invention, the disease is a tumor of the pancreas, pancreatic adenocarcinoma, tumor of the head, body, tail, pancreatic duct, islets of Langerhans, or neck of the pancreas, prostate tumor, prostate cancer, prostate, neuroendocrine tumor, breast cancer, central breast, upper medial quarter of the breast, lower medial quarter of the breast, upper lateral quarter of the breast, lower lateral quarter of the breast, axillary process of the breast, tumor of multiple lesions of the breast, juvenile breast cancer, parathyroid tumor, myeloma, lung cancer, small cell lung cancer, non-small cell lung cancer, tumor of the main bronchus, upper lobe of the lung, middle lobe of the lung, or lower lobe of the lung, colorectal cancer, ascending colon, or colon. Hepatic flexure, transverse colon, splenic flexure of the colon, descending colon, sigmoid colon, multiple lesions of the colon, tumors of the small intestine, liver tumors, hepatocellular adenoma, hepatocellular carcinoma, hepatocellular cholangiomas, mixed type of hepatocellular carcinoma and cholangiocarcinoma (ombined), hepatoblastoma, ovarian cancer, sarcoma, osteosarcoma, fibrosarcoma, gastrointestinal stromal tumors, gastrointestinal tract, gastric cancer, thyroid cancer, medullary thyroid carcinoma, thyroid gland, renal cell carcinoma, renal pelvis, bladder tumors, bladder cancer, bladder trigone, bladder apex, bladder lateral wall, bladder posterior wall, ureteral orifice, urachus tumors, multiple lesions of the bladder, basal cell carcinoma, basal cell neoplasm, basal cell tumor, basal cell carcinoma, multicentric basal cell Basal cell carcinoma, basal cell carcinoid, basal cell adenoma, squamous cell carcinoma, oral squamous cell carcinoma, laryngeal squamous cell carcinoma, cervical cancer, extracervical tumors, multiple lesions of the cervix, tumors of the cervix, tumors of the isthmus of the uterus, uterine tumors, ovarian tumors, cervical esophagus, thoracic esophagus, abdominal esophagus, upper third of the esophagus, middle third of the esophagus, lower third of the esophagus, tumors of multiple lesions of the esophagus, endometrial cancer, head and neck cancer, lymphoma, malignant mesothelioma, mesothelial neoplasm, mesothelioma, fibrous mesothelioma, fibrous mesothelioma, epithelioid mesothelioma, epithelial mesothelioma, duodenal cancer, neuroendocrine tumors, neuroendocrine tumors of the lung, pancreatic The group is selected from the following: neuroendocrine tumors of the viscera, neuroendocrine tumors of the foregut, neuroendocrine tumors of the midgut, neuroendocrine tumors of the hindgut, gastrointestinal and pancreatic neuroendocrine tumors, neuroendocrine carcinoma, neuroendocrine tumors of the breast, neuroendocrine tumors of the ovary, testicular cancer, thymic carcinoma, tumors of the stomach, gastric fundus, gastric body, gastric antrum, pylorus, lesser curvature of the stomach, greater curvature of the stomach, tumors of overlapping lesions of the stomach, paraganglioma, gangliomas, melanoma, malignant melanoma, nodular melanoma, melanin-deficient melanoma, superficial spreading melanoma, epithelioid cell melanoma, spindle cell melanoma, mixed epithelioid and spindle cell melanoma.

[0628] In further embodiments, the above symptoms include the lateral upper lip, lateral lower lip, unspecified lateral lip, upper lip mucosa, lower lip mucosa, unspecified lip mucosa, lip commissure, overlapping lesions of the lip, unspecified base of the tongue, unspecified dorsal surface of the tongue, tongue margin, unspecified ventral surface of the tongue, unspecified anterior 2 / 3 of the tongue, tonsils, overlapping lesions of the tongue, unspecified tongue, upper gingiva, lower gingiva, unspecified gingiva, anterior floor of the mouth, lateral floor of the mouth, overlapping lesions of the floor of the mouth, unspecified floor of the mouth, hard palate, unspecified soft palate, uvula, Duplicate lesions of the palate, unspecified palate, buccal mucosa, oral vestibule, posterior molar region, other and unspecified parts of the oral cavity, unspecified oral cavity, parotid gland, submandibular gland, sublingual gland, duplicate lesions of major salivary glands, unspecified major salivary glands, tonsillar fossa, trabecula, duplicate lesions of tonsils, unspecified tonsils, fossa, anterior surface of the epiglottis, lateral oropharynx, posterior oropharynx, branchial cleft, duplicate lesions of the oropharynx, unspecified oropharynx, superior nasopharynx, posterior nasopharynx, lateral nasopharynx, anterior nasopharynx, Duplicate lesions of the nasopharynx, unspecified nasopharynx, piriform sinus, postcricosal region, hypopharyngeal surface of the aryepiglottic fold, posterior wall of the hypopharynx, duplicate lesions of the hypopharynx, unspecified hypopharynx, unspecified pharynx, pharynx, larynx, Walder's ring, lips, oral cavity and pharynx, cervical esophagus, thoracic esophagus, abdominal esophagus, upper third of the esophagus, middle third of the esophagus, lower third of the esophagus, duplicate lesions of the esophagus, unspecified esophagus, unspecified cardia, gastric fundus, gastric body, gastric antrum, pylorus, specified Unidentified lesser curvature of the stomach, unidentified greater curvature of the stomach, overlapping lesions of the stomach, unidentified stomach, duodenum, jejunum, ileum, Meckel's diverticulum, overlapping lesions of the small intestine, unidentified small intestine, cecum, appendix, ascending colon, hepatic flexure of the colon, transverse colon, splenic flexure of the colon, descending colon, sigmoid colon, overlapping lesions of the colon, unidentified colon, rectosigmoid junction, unidentified rectum, unidentified anus, anal canal, cloacal layer, overlapping lesions of the rectoanus and anal canal, liver, intrahepatic bile ducts, gallbladder, extrahepatic bile ducts, Vater's ampulla, duplicate lesions of the bile duct, unspecified bile duct, pancreatic head, pancreatic body, pancreatic tail, pancreatic duct, islets of Langerhans, pancreatic neck, duplicate lesions of the pancreas, unspecified pancreas, unspecified intestinal tract, duplicate lesions of the digestive system, unspecified gastrointestinal tract, nasal cavity, middle ear, maxillary sinus, ethmoid sinus, frontal sinus, sphenoid sinus, duplicate lesions of accessory sinuses, unspecified accessory sinuses, glottis, supraglottis, subglottis, laryngeal cartilage, duplicate lesions of the larynx, unspecified larynx, trachea, main bronchus, upper lobe of the lung, middle lobe of the lung, lower lobe of the lung, duplicate lesions of the lung, unspecified lung, thymus, heart, anterior mediastinum, posterior mediastinum, unspecified mediastinum, unspecified pleura, duplicate lesions of the cardiac mediastinum and pleura, Overlapping lesions of the upper respiratory tract, respiratory system and intrathoracic organs that cannot be specified, overlapping lesions of the upper respiratory tract, upper limb long bone joints, upper limb short bone joints, lower limb long bone joints, lower limb short bone joints, overlapping lesions of the bones and articular cartilage of the limbs that cannot be specified, limb bones that cannot be specified, skull and facial bones, mandible, spine, ribs, sternum, clavicle, pelvic bones, overlapping lesions of bones and articular cartilage of the bones that cannot be specified, bones that cannot be specified, blood, bone marrow, spleen, reticuloendothelial system that cannot be specified, hematopoietic system that cannot be specified, skin of the lips that cannot be specified, eyelids that cannot be specified, outer ear, skin of the face, skin of the scalp and neck, skin of the torso, skin of the upper limbs, skin of the lower limbs, peripheral nerves of the head and neck, peripheral nerves of the shoulder and arm, peripheral nerves of the legs, peripheral nerves of the chest Peripheral nerves, peripheral nerves of the abdomen, peripheral nerves of the pelvis, peripheral nerves of the torso, overlapping lesions of the peripheral and autonomic nervous systems, autonomic nervous system unspecified, retroperitoneum, peritoneum, peritoneum unspecified, overlapping lesions of the retroperitoneum and peritoneum, connective tissue of the head, connective tissue of the arms, connective tissue of the legs, connective tissue of the chest, connective tissue of the abdomen, connective tissue of the pelvis, connective tissue of the torso unspecified, overlapping lesions of subcutaneous connective tissue and other soft tissues, connective tissue unspecified, nipple, central part of the breast, upper medial quarter of the breast, lower medial quarter of the breast, upper lateral quarter of the breast, lower lateral quarter of the breast, axillary process of the breast, overlapping lesions of the breast , unspecified breast, labia majora, labia minora, clitoris, overlapping lesions of the vulva, unspecified vulva, unspecified vagina, cervix, external cervix, overlapping lesions of the cervix, cervix, isthmus of the uterus, endometrium, myometrium, fundus, overlapping lesions of the uterine body, uterine body, unspecified uterus, ovary, ductus of Fallopius, broad ligament of the uterus, round ligament, parauterine connective tissue, uterine adnexa, Wolff's body, overlapping lesions of the female reproductive organs, unspecified female reproductive duct, penile foreskin, glans penis, penile body, overlapping lesions of the penis, unspecified penis, prostate, undescended testis, descending testis, unspecified testis, epididymis, spermatic cord, unspecified scrotum, testicular tunica vaginalis,Duplicate lesions of the male genitalia, unspecified male genitalia, unspecified kidneys, renal pelvis, ureters, bladder trigone, bladder apex, bladder lateral wall, bladder posterior wall, ureteral orifice, urachus, duplicate lesions of the bladder, unspecified bladder, urethra, accessory urethral glands, duplicate lesions of the urinary tract, unspecified urinary system, conjunctiva, unspecified cornea, retina, choroid, ciliary body, lacrimal gland, unspecified orbit, duplicate lesions of the eye and adnexa, unspecified eye, meninges, spinal cord, unspecified meninges, cerebrum, frontal lobe, temporal lobe, parietal lobe, occipital lobe, unspecified ventricles, unspecified cerebellum, brainstem, duplicate lesions of the brain, unspecified brain, spinal cord, cauda equina, olfactory nerve, optic nerve, auditory nerve, unspecified cranial nerve, brain and central nervous system It may occur in organs and tissues selected from the group including overlapping lesions of the nervous system, unspecified nervous system, thyroid gland, adrenal cortex, adrenal medulla, unspecified adrenal gland, parathyroid gland, pituitary gland, craniopharyngopharyngeal duct, pineal gland, carotid body, aortic body, endocrine glands and related structures, unspecified endocrine glands, unspecified face or neck, unspecified chest, unspecified abdomen, unspecified pelvis, unspecified upper limb, unspecified lower limb, other unspecified sites, overlapping lesions in unspecified sites, lymph nodes of the face, head and neck, intrathoracic lymph nodes, intraabdominal lymph nodes, axillobracranial lymph nodes, inguinal leg lymph nodes, pelvic lymph nodes, lymph nodes in multiple regions, lymph nodes of unspecified origin, and unknown primary site.

[0629] Subjects treated with the compounds disclosed and claimed herein can be treated in combination with other non-surgical antiproliferative (e.g., anticancer) drug therapies. In one embodiment, the compounds may be administered in combination with anticancer compounds such as cell growth inhibitors. Cell growth inhibitors are compounds (e.g., small molecules, nucleic acids, or proteins) that inhibit cell growth and / or proliferation. In some embodiments, the cell growth inhibitors are directed against malignant cells of a tumor. In yet other embodiments, the cell growth inhibitors inhibit the growth and / or proliferation of vascular smooth muscle cells or fibroblasts.

[0630] Suitable antiproliferative or cell proliferation inhibitory compounds for use with the compounds disclosed and claimed herein include anticancer drugs. While anticancer drugs are well known and not limited to, the following are examples: Asibicin; Akurarubicin; Acodazole hydrochloride; Acronin; Adzeresin; Aldesleukin; Altoretamine; Ambomycin; Amethantrone acetate; Aminoglutethimide; Amsacrin; Anastrozole; Anthramycin; Asparaginase; Asperlin; Azacitidine; Azetepa; Azotomycin; Batymastam; Benzodepa; Bicalutamide; Bisanthren hydrochloride; Bisnafide dimesylate; Bizeresin; Bleomycin sulfate; Brequinal sodium; Bropyrimine; Bus Rufan; Cactinomycin; Carsterone; Calasemide; Carvetimer; Carboplatin; Carmustine; Carbicin hydrochloride; Carzeresin; Sedefingol; Chlorambucil; Ciloremycin; Cisplatin; Cladribine; Cristonal mesylate; Cyclophosphamide; Cytarabine; Dacarbazine; Dactinomycin; Daunorubicin hydrochloride; Decitabine; Dexormaplatin; Dezaguanine; Dezaguanine mesylate; Diaziquan; Docetaxel; Doxorubicin; Doxorubicin hydrochloride; Doroxifene; Doroxifene citrate; P Dromostanolone lopionate; duazomycin; edatrexate; eflornithine hydrochloride; erusamitrusin; enloplatin; empromate; epipropidine; epirubicin hydrochloride; erbrozol; esorubicin hydrochloride; estramustine; estramustine sodium phosphate; etanidazole; etoposide; etoposide phosphate; etopurine; fadrozol hydrochloride; fazarabine; fenretinide; floxuridine; fludarabine phosphate; fluorouracil; flurocitabine; fosquidone; fostriersin sodium; gemcitabine; Gemcitabine hydrochloride; hydroxyurea; idarubicin hydrochloride; ifosfamide; irmofosin; interferon alpha-2a; interferon alpha-2b; interferon alpha-n1; interferon alpha-n3; interferon beta-1a; interferon gamma-1b; iproplatin; irinotecan hydrochloride; lanreotide acetate; letrozole; leuprolide acetate; rialozol hydrochloride; lometrexol sodium; lomustine; losoxantrone hydrochloride; masopropyl alcohol; mytansine; mechloretamine hydrochloride;Megestrol acetate; Melengestrol acetate; Melphalan; Menogalil; Mercaptopurine; Methotrexate; Methotrexate sodium; Metoprin; Metsuredepa; Mitindomide; Mitocalcin; Mitochromin; Mitogiline; Mitomarcin; Mitomycin; Mitospar; Mitotan; Mitoxantrone hydrochloride; Mycophenolic acid; Niraparib; Nocodazole; Nogaramycin; Olparib; Olmaplatin; Oxythran; Paclitaxel; Pegaspargaze Periomycin; Pentamustine; Peplomycin sulfate; Perphosphamide; Pipobroman; Piposulfan; Pyroxantrone hydrochloride; Plicamycin; Promestan; Porfimer sodium; Porfiromycin; Prednimustine; Procarbazine hydrochloride; Puromycin; Puromycin hydrochloride; Pyrazofrine; Ribopurine; Logretimide; Lucaparib; Safingol; Safingol hydrochloride; Semustine; Simtrazene; Sparphosate sodium ;Sparsomycin;Spirogermanium hydrochloride;Spiromustine;Spiroplatin;Streptonigrin;Streptozocin;Slofenul;Talazoparib;Tarisomycin;Taxol;Taxotere;Tecogalan sodium;Tegafur;Teloxantrone hydrochloride;Temoporfin;Teniposide;Teloxylone;Testolactone;Thiamipurine;Thiogunine;Thiotepa;Thiazofrine;Tirapazamine;Topotecan hydrochloride;Tremifene citrate;Trestron acetate Examples include trisilibine phosphate, trimethrexate, trimethrexate glucuronide, tuburozole hydrochloride, uracil mustard, uredepa, bapreotide, veraparib, verteporfin, vinblastine sulfate, vincristine sulfate, vindesine, vindesine sulfate, vinepidine sulfate, vinricinate sulfate, vinoleulosine sulfate, vinorelbine tartrate, vinrosidine sulfate, vinzolidine sulfate, borozol, zeniplatin, dinostatin, and zolubicin hydrochloride.

[0631] Other anticancer drugs include, but are not limited to, 20-epi-1,25-dihydroxyvitamin D3; 5-ethinyluracil; abiraterone; acylfluben; adesipeno Adzelesin; ALL-TK antagonist; Ambamustin; Amidox; Amiphostin; Aminolevulinic acid; Amrubicin; Anagrelide; Androgravoride; Angiogenesis inhibitor; Antagonist D; Antagonist G; Antarelix; Anti-dorsalizing morphogenetic protein-1; Anti-estrogen; Antineoplaston; Antisense oligonucleotide; Aphydicolinglycinate; Apoptosis gene modulator; Apoptosis regulator; Aprinic acid; ara-CDP-DL-PTBA; Arginine deaminase; Asracrin; Atamestan; Atrimustin; Axinastatin 1; Axinastatin 2; Axinastatin 3; Azasetron; Azatoxin; Azatyrosine; Baccatin III derivative; Varanol; Batymast; BCR / ABL antagonists; benzochlorine; benzoyl staurosporine; beta-lactam derivatives; beta-aretin; betacramycin B; betulinic acid; bFGF inhibitors; bisaziridinylspermine; bisnafide; bistratin A; breflate; budotitanium; butionine sulfoximine; calcipotriol; carphostin C; camptothecin derivatives; canariapox IL-2; capecitabine; carboxamide-amino-triazole; carboxyamide triazole; CaRest M3; CARN 700; cartilage-derived inhibitors; casein kinase inhibitors (ICOS); castanospermine; cecropin B; cetrorelix; chlorine; chloroquinoxaline sulfonamide; cicaprost; cis-porphyrin; clomiphene analogs; clotrimazole; colismycin A; colismycin B; combretastatin A4; combretastatin analogs; conagenin; crambecydin 816; cristinator; cryptophycin 8; cryptophycin A derivatives; curacin A; cyclopentaanthraquinone; cycloplatam; cypemycin; cytarabine ocphosphate; cytolytic factors; cytostatin; dacliximab; dehydrodydemnin B; deslorerin; dexphosphamide; dexrazoxane; dexverapamil; didemnin B; zidox; diethylnorspermine; dihydro-5-azacitidine;9-Dihydrotaxol (9-); Dioxamycin; Diphenylspiromustine; Docosanol; Dracetron; Doxifluridine; Dronabinol; Duocalmycin SA; Ebselen; Ecomustine; Edelfosine; Edrecolomab; Eflomitin; Elemen; Emiteflu; Epirubicin; Epristeride; Estramustine analog; Estrogen agonist; Estrogen antagonist; Etanidazole; Etoposide phosphate; Exemestane; Filgrastim; Finasteride; Flavopyridol; Fresse Rustin; Fluasterone; Fludarabine; Fluorodaunornicin hydrochloride; Forphenimex; Formestan; Fotemustine; Gadolinium texaphylline; Gallium nitrate; Gallocitabine; Ganirelix; Gelatinase inhibitors; Glutathione inhibitors; Hepsulfame; Helegulin; Hexamethylene bisacetamide; Hypericin; Ibandronate; Idoxifen; Idramanton; Irmofosin; Ilostat; Imidazoacridone; Imiquimod; Immunostimulating peptides; Insulin-like growth factor-I receptor inhibitors; Interferon agonists; Interferon; Interleukin; Iobengan; Iododoxorubicin; 4-Ipomeanol; Irinotecan; Iropract; Ilsogladine; Isobengazole; Isohomohalichondrin B; Itasetron; Jasplakinol; Kahalalid F; Lamelalin-N Triacetate; Lanreotide; Reinamycin; Renograstim; Lentinan Sulfate; Leptolstatin; Leukemia Suppressor; Leukocyte Alpha Interferon; Leuprolide + Estrogen + Progesterone; Leuprorelin; Lebamisol; Rialozol L-type; linear polyamine analogs; lipophilic disaccharide peptides; lipophilic platinum compounds; lysoclinamide 7; lovaplatin; rombrisin; lometrexol; ronidamin; losoxantrone; lovastatin; loxolibine; lutetecan; lutetium texaphylline; lysophylline; soluble peptides; mytansin; mannostatin A; marimastat; masopropyl; maspin; matrilysin inhibitors; matrix metalloproteinase inhibitors; melbaron; meterelin; methioninase; metoclopramide; MIF inhibitors; mifepristone; miltefosine;Millimostim; mismatched double-stranded RNA; mitogwazo; Mitractol; Mitomycin analog; Mitonafide; Mitotoxin fibroblast growth factor-saporin; Mophalotene; Monoclonal antibody, human chorionic gonadotropin; Monophosphoryl lipid A + Mycobacterium cell wall SK; Mopidamole; Multidrug resistance gene inhibitor; Therapy based on multiple tumor suppressor 1; Mustard anticancer compound; Mycaperoxide B; Mycobacterial cell wall extract; Myriapolon; N-acetyldinaline; N-substituted benzamide; Nafarelin; Naglestipp; Naloxone + Pen Tazosin; Napavin; Naphterpine; Naltgrastim; Nedaplatin; Nemorubicin; Neridronic acid; Neutral endopeptidase; Niltamide; Nisamycin; Nitric oxide modulator; Nitroxide antioxidant; Nitrulline; O6-benzylguanine; Octreotide; Oxenon; Oligonucleotide; Onapristone; Ondansetron; Ondansetron; Oracin; Oral cytokine inducer; Osateron; Oxaliplatin; Oxaunomycin; Paclitaxel analog; Paclitaxel derivative; Paraamine; Palmitoyl rhizoxine; Pami Dronic acid; Panaxytriol; Panomiphene; Parabactin; Pazeliptin; Pegaspargase; Perdecine; Pentosan polysulfate sodium; Pentostatin; Pentrozole; Perflubron; Perphosphamide; Periryl alcohol; Phenazinomycin; Phenylate; Phosphatase inhibitor; Picibanil; Pilocarpine hydrochloride; Pirarubicin; Pyritrexime; Placetin A; Placetin B; Plasminogen activator inhibitor; Platinum complex; Platinum compound; Platinum-triamine complex; Porfimer sodium; Porphyromycin; P Ropirubis-acridone; prostaglandin J2; proteasome inhibitors; protein A-based immune modulators; protein kinase C inhibitors; protein kinase C inhibitors (multiple); microalgae; protein tyrosine phosphatase inhibitors; purine nucleoside phosphorylase inhibitors; purpurin; pyrazoloacridine; pyridoxylated hemoglobin polyoxyethylene conjugate; raf antagonists; larcitrexed; ramosetron; ras farnesyl protein transferase inhibitors; ras inhibitors; ras-GAP inhibitors;Demethylated retelliptin; rhenium etidronate (Re186); rhizoxin; ribozyme; RII retinamide; rohitzkin; romulutide; lokinimex; rubiginone B1; ruboxyl; saintopine; SarCNU; sacrophytol A; salglamostim; Sdi1 mimetic; aging-derived inhibitor 1; sense oligonucleotide; signaling inhibitor; signaling modulator; single-chain antigen-binding protein; schizofuran; sobuzoxane; sodium borocane Butate; sodium phenylacetate; sorbel; somatomedin-binding protein; sonelmin; sparfosinic acid; spicamycin D; spiromustin; sprenopentin; spongistatin 1; squalamine; stem cell inhibitor; stem cell division inhibitor; stipamide; stromelysin inhibitor; sulfinosine; hyperactive vasoactive intestinal peptide antagonist; sladista; slamin; swainsonin; synthetic glycosaminoglycan; talimustin; tamoxifen methi Ozide; Tauromustine; Tazarotene; Tecogalan sodium; Tegafur; Telrapillium; Telomerase inhibitor; Temozolomide; Tetrachlorodecaoxide; Tetrazomine; Talibrasticin; Thalidomide; Thiocorallin; Thrombopoietin; Thrombopoietin mimetic; Thymalfacin; Thymopoietin receptor agonist; Thymotrinan; Thyroid-stimulating hormone; Ethyl etioplurids; Titanocene dichloride; Topsentin; Toremifene; Totipotent stem Cellular factors; translation inhibitors; tretinoin; triacetyluridine; trisilibine; tropisetron; tulosteride; tyrosine kinase inhibitors; thyrophostine; UBC inhibitors; ubenimex; urogenital sinus-derived growth inhibitors; urokinase receptor antagonists; variolin B; vector systems, erythrocyte gene therapy; velaresol; veramine; verazine; vinorelbine; vinxaltin; vitaxin; zanoterone; zirascorb; and dinostatin stimalamers.

[0632] The compounds disclosed herein and claimed may also be used in combination with any of the following treatments: Poly(ADP) is a class of chemotherapy agents that target cancers with DNA damage repair deficiencies. Therapies combined with ribose polymerase (PARP) inhibitors (Yuan et al., Expert Opin Ther Pat, 2017, 27:363). Examples of such PARP inhibitors include, but are not limited to, olaparib, rupacarib, veraparib, niraparib, talazoparib, pamiparib, iniparib, E7449, and A-966492.

[0633] For example, therapies combining inhibitors of signaling pathways and mechanisms that lead to the repair of single- and double-strand breaks in DNA, such as nuclear factor-kappa B signaling (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, those of ATM and ATR kinases, checkpoint kinases 1 and 2, DNA-dependent protein kinases, and WEE1 kinase (Pilie et al., Nat Rev Clin Oncol, 2019, 16:81).

[0634] 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 that can bind to tumor cells and / or metastases and induce antibody-dependent cell-mediated 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 Therapies that combine therapies 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) with cell therapy. Immune checkpoint inhibitors include, but are not limited to, nivolumab, ipilimumab, pembrolizumab, atezolizumab, avelumab, durvalumab, and cemiplimab.

[0635] According to the present invention, the compound can be administered before, simultaneously with, or after other anticancer compounds. The administration schedule may include administering different drugs in an alternating manner. In other embodiments, the compound may be delivered before and between, between and after, or before and after, treatment using other therapies. In some cases, the compound is administered more than 24 hours before the administration of other antiproliferative treatments. In other embodiments, the compound may be administered to a subject in combination with more than one antiproliferative therapy. For example, a subject may receive the compound of the present invention in combination with both surgery and at least one other antiproliferative compound. Alternatively, the compound may be administered in combination with more than one anticancer drug.

[0636] In one embodiment, the compounds of the present invention are used to detect cells and tissues that overexpress FAP, thereby achieving such detection by conjugating a detectable label, preferably a detectable radionuclide, to the compounds of the present invention. In a preferred embodiment, the cells and tissues to be detected are diseased cells and tissues, and / or are one or the sole cause of the disease and / or symptoms of the disease, or are part of the pathology underlying the disease. In a further preferred embodiment, the diseased cells and tissues are those that cause and / or are part of a tumor adaptation (e.g., neoplasms, tumors, and cancer) or a non-tumor adaptation (e.g., inflammatory diseases, cardiovascular diseases, autoimmune diseases, and fibrotic diseases).

[0637] In another embodiment, the compounds of the present invention are used to treat cells and tissues that overexpress FAP. In a preferred embodiment, the cells and tissues to be treated are diseased cells and tissues, and / or are one or the sole cause of the disease and / or symptoms of the disease, or are part of the pathology underlying the disease. In a further preferred embodiment, the diseased cells and tissues are causing and / or part of a tumor adaptation (e.g., neoplasms, tumors, and cancer), and therapeutic activity is achieved by conjugating a therapeutically active effector, preferably a therapeutically active radionuclide, to the compounds of the present invention. In a further preferred embodiment, the diseased cells and tissues are causing and / or part of a non-tumor adaptation (e.g., inflammatory diseases, cardiovascular diseases, autoimmune diseases, and fibrotic diseases), and therapeutic activity is achieved by inhibiting the enzymatic activity of FAP.

[0638] In further embodiments, particularly when the disease is a non-tumor disease or non-tumor indication (e.g., inflammatory diseases, cardiovascular diseases, autoimmune diseases, and fibrotic diseases), the compounds of the present invention are administered in a therapeutically effective dose; preferably, the compounds of the present invention do not contain therapeutically active radioisotopes. The effective dose is a dose of the compound sufficient to produce a therapeutically or medically desirable result or effect in the subject to which the compound is administered. The effective dose will vary depending on 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 concurrent or concomitant therapies (if any), the specific route of administration, and factors within the scope of the knowledge and expertise of the healthcare professional. For example, in relation to a method directed toward treating a subject having a condition characterized by abnormal cell proliferation, the effective dose for inhibiting proliferation would be a dose sufficient to reduce or completely halt abnormal cell proliferation in order to slow or stop the development or progression of cell masses such as tumors. As used in these embodiments, “inhibit” encompasses all of the above.

[0639] In other embodiments, the therapeutically effective dose would be the amount necessary to prolong the dormancy of micrometastases or to stabilize residual primary tumor cells after surgery or drug therapy. Generally, when using non-conjugated compounds that do not contain therapeutically active radionuclides, the effective therapeutic dose varies depending on the age, condition, and sex of the subject, as well as the nature and severity of the disease in the subject, all of which can be determined by a person skilled in the art. The dosage may be adjusted by the individual physician or veterinarian, particularly in the event of complications. The effective therapeutic dose is typically, but is not limited to, amounts ranging from 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, in one or more doses per day over one or more days. If necessary, the effective daily dose of the active compound may be administered as two, three, four, five, six, or more lower doses, for example, separately administered at appropriate intervals throughout the day, in unit dosage forms as needed. In some embodiments, the compound is administered for longer than 7 days, longer than 10 days, longer than 14 days, and longer than 20 days. In yet other embodiments, the compound is administered over several weeks or months. In yet another embodiment, the compound is delivered every other day. For example, the drug is delivered every two days, or every three days, or every four days, or every five days, or every six days, or weekly, or monthly.

[0640] In preferred embodiments, the compounds of the present invention are for use in the treatment and / or prevention of diseases, thereby such treatment being radionuclide therapy. Preferably, radionuclide therapy utilizes or is based on different forms of radiation emitted by radionuclides. Such radiation may include, for example, photon radiation, but is not limited to beta radiation. - The radiation may be any one of the following: radiation of particles and electrons including Auger electrons, proton radiation, neutron radiation, positron radiation, alpha particle radiation, or an ion beam. Depending on the type of radiation, radionuclide therapy can be distinguished, for example, as photon-based radionuclide therapy, electron-based radionuclide therapy, proton-based radionuclide therapy, neutron-based radionuclide therapy, positron-based radionuclide therapy, alpha-particle-based radionuclide therapy, or ion-beam-based radionuclide therapy. All of these forms of radionuclide therapy are encompassed by the present invention, and all of these forms of radionuclide therapy can be realized by the compounds of the present invention, preferably under the condition that the radionuclides attached to the compounds of the present invention provide this type of radiation, more preferably as effectors.

[0641] Radionuclide therapy preferably works by damaging the DNA of cells. Damage is caused by photons, electrons, protons, neutrons, positrons, alpha particles, or ion beams that directly or indirectly ionize the atoms that make up the DNA strands. Indirect ionization occurs as a result of the ionization of water, damaging the DNA after forming free radicals, notably hydroxyl radicals.

[0642] In the most common forms of radionuclide therapy, much of the effect of radiation is due to free radicals. Since cells have mechanisms to repair DNA damage, cutting DNA on both strands proves to be the most significant technique in altering cellular properties. Cancer cells are generally undifferentiated and stem cell-like, so they replicate more and have a reduced ability to repair non-lethal damage compared to many healthy differentiated cells. DNA damage is inherited through cell division, causing the damage to accumulate in cancer cells, leading to their death or slower replication.

[0643] Oxygen is a powerful radiosensitizer, increasing the effectiveness of a given dose of radiation by forming DNA-damaging free radicals. Therefore, the use of hyperbaric oxygen tanks, blood substitutes that carry large amounts of oxygen, hypoxic cytoradiosensitizers such as misonidazole and metronidazole, and hypoxic cytotoxins such as tirapazamine can be applied.

[0644] Other factors to consider when selecting the radioactive dose include whether the patient is receiving chemotherapy, whether radiotherapy is administered before or after surgery, and the degree of surgical success.

[0645] The total radioactive dose can be divided, i.e., spread over time as one or more treatments, for several important reasons. Dividing gives normal cells time to recover, while tumor cells generally have a lower efficiency of repair between divided doses. Dividing also allows tumor cells that were in a relatively radioresistant phase of the cell cycle during a single treatment to cycle back into the sensitive phase before the next divided dose is administered. Similarly, tumor cells that were chronically or acutely hypoxic and therefore more radioresistant may reoxidize between divided doses, improving tumor cell killing.

[0646] It is generally known that different cancers respond differentially to radiotherapy. The response of cancer to radiation is described by its radiosensitivity. Highly radiosensitive cancer cells are rapidly killed by moderate doses of radiation. These include leukemia, mostly lymphoma, and germ cell tumors.

[0647] To some extent, it is important to distinguish the radiosensitivity of a particular tumor, which is a measured value in laboratory tests, from the "cureability" of the cancer based on the internally delivered dose of radioactive material in actual clinical practice. For example, leukemia is generally not curable with radiotherapy because it is scattered throughout the body. Lymphoma may be curable with radiation if it is localized to one area of ​​the body. Similarly, many common moderately radioresponsive tumors can be treated with a curative dose of radioactive material if they are in the early stages. This is, for example, non-melanoma skin cancer, head and neck cancer. This applies to cancer, non-small cell lung cancer, cervical cancer, anal cancer, and prostate cancer.

[0648] The response of a tumor to radiotherapy is also related to its size. For complex reasons, very large tumors respond less to radiation than smaller tumors or microscopic lesions. Various strategies are used to overcome this effect. The most common technique is surgical excision before radiotherapy. This is most commonly seen in the treatment of breast cancer using broad mastectomy or mastectomy, followed by adjuvant radiotherapy. Another method is to shrink the tumor using neoadjuvant chemotherapy before radionuclide therapy. A third technique is to enhance the radiosensitivity of the cancer by administering certain drugs during the course of radiotherapy. Examples of radiosensitizers, but not limited to, include cisplatin, nimorazole, and cetuximab.

[0649] Intraoperative radiotherapy is a specialized type of radiotherapy delivered immediately after the surgical removal of cancer. This method has been used in breast cancer (targeted intraoperative radiotherapy), brain tumors, and rectal cancer.

[0650] Radionuclide therapy is painless in itself. Many low-dose palliative treatments have little or no effect. Higher-dose treatments can cause side effects that change during treatment (acute side effects), after treatment within months or years (long-term side effects), or after retreatment (cumulative side effects). The nature, severity, and persistence of side effects depend on the organ being irradiated, the treatment itself (type of radionuclide, dose, fractionation, concurrent chemotherapy), and the patient.

[0651] It is within the scope of the present invention that each and any of the above strategies can be realized insofar as the methods for treating the diseases of the present invention are known in the art as such and constitute further embodiments of the present invention.

[0652] Furthermore, the compounds of the present invention may also be used in methods for the diagnosis of diseases disclosed herein. Such methods preferably include the step of administering a diagnostically effective amount of the compounds of the present invention to a subject requiring it.

[0653] According to the present invention, the imaging method is selected from the group consisting of scintigraphy, single-photon emission computed tomography (SPECT), and positron emission (PET). In preferred embodiments of the present invention, compounds according to the present invention comprising a chelating agent derived from the N4 chelating agent family, more preferably a chelating agent for Tc radionuclides, are particularly suitable for use in methods and procedures using SPECT. In these embodiments, the chelating agent derived from the N4 chelating agent family is N4Ac.

[0654] In preferred embodiments of the present invention, compounds according to the present invention that include a NODAGA chelating agent, and more preferably chelate Ga radionuclides, are particularly suitable for use in methods and procedures using PET.

[0655] 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, preferably internalized 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. For this reason, SPECT and PET are classified as separate techniques from scintigraphy, although they also use a gamma camera to detect internal radiation. Scintigraphy differs from diagnostic X-rays, in which external radiation passes through the body to form an image.

[0656] Single-photon emission tomography (SPECT) scanning is a type of nuclear imaging technique that uses gamma rays. They are very similar to conventional nuclear medicine two-dimensional imaging that uses a gamma camera. Before a SPECT scan, the patient is injected with radiolabeled chemi-emitting gamma rays that can be detected by the scanner. A computer collects information from the gamma camera and converts it into two-dimensional cross-sections. These cross-sections can be added together to reconstruct a three-dimensional image of an organ or tissue. SPECT involves detecting gamma rays emitted by radionuclides provided by radiolabeled chemicals, both individually and sequentially. To acquire SPECT images, the gamma camera is rotated around the patient. Projection images are acquired at predetermined points during rotation, typically every 3–6°. Often, a full 360° rotation is used to obtain optimal reconstruction. The time taken to acquire each projection image also varies, but is typically 15–20 seconds. This gives a total scanning time of 15–20 minutes. Multi-head gamma cameras are faster. SPECT acquisition is very similar to 2D gamma camera imaging, so the same radiopharmaceuticals can be used.

[0657] Positron emission tomography (PET) is a non-invasive diagnostic imaging technique for measuring the biochemical state or metabolic activity of cells in the human body. PET is unique because it produces images of the fundamental biochemistry or function within the body. Traditional diagnostic techniques such as X-rays, CT scans, or MRI produce images of the body's biological structures or structures. The premise of these techniques is that they allow us to see changes in structures or biological structures associated with disease. Biochemical processes are also altered by disease and can occur before overall changes in biological structures. PET is an imaging technique that can visualize some of these early biochemical changes. A PET scanner relies on radiation emitted from the patient to create images. Each patient is given a small amount of a radiopharmaceutical that is very similar to a natural substance used by the body or that specifically binds to a receptor or molecular structure. As the radioactive isotope undergoes positron emission decay (also known as beta-plus decay), it emits a positron, the antiparticle counterpart of the electron. After traveling up to a few millimeters, a positron encounters an electron, annihilates, and travels in the opposite direction, producing a pair of annihilation (gamma) photons. These are detected when they reach the scintillation material in the scanning device, producing a burst of light which is detected by a photomultiplier tube or silicon avalanche photodiode. This technique relies on the simultaneous or coincident detection of photon pairs. Photons that do not arrive as a pair, i.e., within a few nanoseconds, are ignored. All matches are forwarded to an image processing unit, where the final image data is produced using an image reconstruction procedure.

[0658] SPECT / CT and PET / CT are combinations of SPECT and PET with computed tomography (CT). A key benefit of combining these modalities is improved reliability and accuracy for the reader. With traditional PET and SPECT, the limited number of photons emitted from the abnormal area result in a very low level of background that is difficult to anatomically localize to that area. The addition of CT helps determine the location of the abnormal area from an anatomical perspective and classify its likelihood of representing a disease.

[0659] It is within the scope of the present invention that each and any of the above strategies can be realized insofar as the methods for diagnosing diseases of the present invention are known in the art as such and constitute further embodiments of the present invention.

[0660] The compounds of the present invention are useful for stratifying patients, that is, for creating subsets within a patient population that provide detailed information about how patients respond to a given drug. Stratification involves identifying a subset of the population most likely to respond to a novel therapy. This could be a crucial component in converting clinical trials resulting from negative or neutral outcomes into those with positive outcomes.

[0661] Stratification involves identifying patient groups that share “biological” characteristics to select the optimal patient management and achieve the best possible outcomes with respect to risk assessment, risk prevention, and achieving optimal treatment outcomes.

[0662] The compounds of the present invention can be used to assess or detect, as quickly as possible, a specific disease (diagnostic use), the risk of developing the disease (susceptibility / risk use), and the progression of the disease, including painless resistance to invasiveness (prognostic diagnostic use), and can be used to predict the response and toxicity to a given treatment (predictive use).

[0663] Furthermore, the use of the compounds of the present invention in diagnostic and therapeutic methods also falls within the scope of the present invention. The concept of diagnostic and therapeutic involves combining a therapeutic agent with a corresponding diagnostic test that can increase the clinical use of the therapeutic agent. The concept of diagnostic and therapeutic is becoming increasingly appealing and is widely considered key to improving the efficiency of drug treatment by helping physicians identify patients who would benefit from a given therapy and thus avoid unnecessary treatments.

[0664] The concept of diagnostic therapy involves combining a therapeutic agent with diagnostic tests that allow a physician to identify patients who would benefit most from a given therapy. In embodiments, and as is preferably used herein, the compounds of the present invention are also used for the diagnosis of a patient, i.e., for the identification and localization of the primary tumor and potential local and distant metastases. Furthermore, tumor volume can be determined, in particular, using a three-dimensional diagnostic modality such as SPECT or PET. Only patients with FAP-positive tumor masses and therefore who would benefit from a given therapy are selected for a particular therapy, thus avoiding unnecessary procedures. Preferably, such a therapy is an FAP-targeted therapy using the compounds of the present invention. In one particular embodiment, chemically identical tumor-targeted diagnostics, preferably imaging diagnostics for scintigraphy, PET or SPECT, and radiotherapy are applied. Such compounds differ only in their radionuclides and are therefore usually very similar, even if not identical in their pharmacokinetic profiles. This can be achieved using chelating agents and diagnostic or therapeutic radiometals. Alternatively, this can be achieved using radiolabeling with precursors for radiolabeling and radionuclides for diagnostic or therapeutic purposes. In one embodiment, diagnostic imaging is preferably used by quantifying the radiation of the diagnostic radionuclide, followed by dosimetry known to those skilled in the art, and prediction of drug concentrations in the tumor compared to vulnerable organs. Thus, truly personalized drug therapy for the patient is achieved.

[0665] In embodiments, and as is also preferred herein, the diagnostic and therapeutic method is implemented using only one diagnostically and therapeutically active compound, such as a compound of the present invention labeled with a radionuclide that emits diagnostically detectable radiation (e.g., positrons or gamma rays) and therapeutically effective radiation (e.g., electrons or alpha particles).

[0666] The present invention also aims to provide a method for intraoperatively identifying / disclosing diseased tissue expressing FAP in a subject. Such a method utilizes the compounds of the present invention, thereby preferably comprising a diagnostically active agent as an effector.

[0667] According to further embodiments of the present invention, the compounds of the present invention, in particular when complexed with radionuclides, are used in radiotherapy, including surgical treatment as a first method for treating many isolated solid cancers, radiotherapy, alkylating agents, antimetabolites, and radioactive materials, including the use of ionizing radiation in attempts to cure or improve cancer symptoms using sealed internal or external light sources in the form of brachytherapy. It can be used as an adjuvant or accessory to any other oncological treatment, including chemotherapy such as anthracyclines, plant alkaloids, topoisomerase inhibitors, and other antitumor agents; hormonal treatments that modulate the behavior of tumor cells without directly attacking them; 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 activities to alleviate physical, emotional, mental, and psychosocial distress to improve the quality of life of patients; and alternative treatments, including a diverse group of products that are not part of the healthcare system, practices, and conventional medicines.

[0668] In embodiments of the method of the present invention, the subject is a patient. In embodiments, the patient is a subject who has been diagnosed with a disease, is suspected of having a disease, has a disease, or is at risk of developing a disease, thereby the disease being one of the diseases described herein, preferably a disease including FAP.

[0669] The doses used in the implementation of the treatment and diagnostic methods, each containing a radionuclide, or more specifically, a compound of the present invention conjugated to or part thereof, will vary depending, for example, on the specific condition to be treated, such as the known radiosensitivity of the tumor type, the tumor volume, and the desired therapy. Generally, the dose is calculated based on the radioactivity distribution to the respective organ and the observed target uptake. The gamma-emitting complex may be administered once or several times for diagnostic imaging. In animals, the indicated dose range is, for example, 1 to 200 MBq. 111 In or 89 The compound of the present invention may be complexed with Zr at a dose of 0.1 μg / kg to 5 mg / kg. The β-releasing complex of the compound 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, the indicated dose range is, for example, 1 to 200 MBq. 90 Y or 177 The compound of the present invention may be complexed with Lu at a dose of 0.1 μg / kg to 5 mg / kg. In larger animals, such as humans, the indicated dose range is, for example, 10 to 400 MBq. 111 In or 89 The compound of the present invention is complexed with Zr at a dose of 0.1 to 100 μg / kg. In larger animals, such as humans, the indicated dose range is, for example, 10 to 5000 MBq. 90 Y or 177 The compound of the present invention is complexed with Lu and is present in a concentration of 0.1 to 100 μg / kg.

[0670] In a further embodiment, the present invention relates particularly to compositions and pharmaceutical compositions comprising the compounds of the present invention. The pharmaceutical composition of the present invention comprises at least one compound of the present invention and, optionally, one or more carriers, excipients, and / or adjuvants. The pharmaceutical composition may further, for example, contain water, a buffer such as neutral buffered saline or phosphate buffered saline, ethanol, mineral oil, vegetable oil, dimethyl sulfoxide, a carbohydrate such as glucose, mannose, sucrose, or dextran, mannitol, protein, adjuvant, amino acids such as polypeptides or glycine, antioxidants, a chelating agent such as EDTA or glutathione, and / or a preservative. Furthermore, although not essential, one or more other active ingredients may be included in the pharmaceutical composition of the present invention.

[0671] The pharmaceutical compositions of the present invention can be formulated for any suitable route of administration, including, for example, topical administration such as transdermal or ocular, oral, buccal, nasal, vaginal, rectal, or parenteral administration. As used herein, the term “parenteral” includes subcutaneous, intradermal, intravascular (such as intravenous), intramuscular, intrathecal, and intraperitoneal injections, as well as any similar injection or infusion techniques. The preferred route of administration is intravenous administration.

[0672] In embodiments of the present invention, the compounds of the present invention, including radionuclides, are administered by any conventional route, particularly intravenously, for example, in the form of an injectable solution or suspension. The compounds of the present invention may be administered, advantageously, by infusion, for example, by an infusion lasting 30 to 60 minutes.

[0673] Depending on the location of the tumor, the compound of the present invention can be administered as close to the tumor site as possible, for example, using a catheter. Such administration can be carried out directly into the tumor tissue, the surrounding tissue, or into afferent blood vessels. The compound of the present invention can also be administered repeatedly in doses, preferably in divided doses.

[0674] According to a preferred embodiment of the present invention, the pharmaceutical composition of the present invention comprises a stabilizer, for example, a free radical scavenger that inhibits the autoradiolysis of the compound of the present invention. Suitable stabilizers include, for example, serum albumin, ascorbic acid, retinol, gentisic acid or its derivatives, or preferably, commercially available amino acid infusion solutions used for parenteral protein delivery, such as Proteinsteril® KE Nephro, which do not contain electrolytes and glucose. Ascorbic acid and gentisic acid are preferred.

[0675] The pharmaceutical composition of the present invention may also contain further additives, such as agents for adjusting the pH to 7.2-7.4, for example, sodium acetate or ammonium acetate or Na2HPO4. Preferably, a stabilizer is added to the non-radioactive compound of the present invention, and the introduction of a radionuclide, for example, complexation with a radionuclide, is carried out in the presence of the stabilizer at room temperature, or preferably at a temperature of 40-120°C. Complexation can be conveniently carried out under air-free conditions, for example, under N2 or Ar. Further stabilizers may be added to the composition after complexation.

[0676] In particular, when the effector is a radionuclide, the excretion of the compounds of the present invention essentially occurs via the kidneys. Further protection of the kidneys from radioactive accumulation can be achieved, in particular when the effector is a radionuclide, by administering lysine or arginine or an amino acid solution having a high content of lysine and / or arginine, such as commercially available amino acid solutions like Synthamin®-14 or -10, before or simultaneously with the injection of the compounds of the present invention. Renal protection can also be achieved by administering a plasma expander, such as gerofsin, instead of or in addition to amino acid infusion. Renal protection can also be achieved by administering a diuretic that provides a means of forced diuresis that increases the rate of urination. Such diuretics include high-ceiling loop diuretics, thiazides, carbonic anhydrase inhibitors, potassium-sparing diuretics, calcium-sparing diuretics, osmotic diuretics, and low-ceiling diuretics. The pharmaceutical composition of the present invention may contain, in addition to the compounds of the present invention, at least one further compound intended for or suitable for kidney protection, preferably kidney protection in the subject to whom the compounds of the present invention are administered.

[0677] Those skilled in the art will understand that the compounds of the present invention are disclosed herein for use in various ways. It will further understand that the compositions and pharmaceutical compositions of the present invention can be used equally in the aforementioned ways. It will also be understood that the compositions and pharmaceutical compositions of the present invention are disclosed herein for use in various ways. Similarly, those skilled in the art will understand that the compounds of the present invention can be used equally in the aforementioned ways.

[0678] Those skilled in the art will recognize that the compositions and pharmaceutical compositions of the present invention contain one or more further compounds in addition to the compounds of the present invention. It will be understood that, to the extent disclosed herein as being part of a method of the present invention, one or more such further compounds may be administered separately from the compound of the present invention to the subject to exposure or to the subject of the method of the present invention. Such administration of one or more further compounds may be carried out before, simultaneously with, or after, the administration of the compound of the present invention. It will also be recognized by those skilled in the art that, in the method of the present invention, one or more further compounds may be administered separately from the compound of the present invention to the subject. Such administration of one or more further compounds may be carried out before, simultaneously with, or after, the administration of the compound of the present invention. To the extent disclosed herein as being administered as part of the method of the present invention, it will be understood that one or more such further compounds are part of the compound of the present invention and / or the pharmaceutical composition of the present invention. It is within the scope of the present invention that the compound of the present invention and one or more further compounds may be contained in the same or different formulations. It is also within the scope of the present invention that the compound of the present invention and one or more further compounds may not be contained in the same formulation, but may be contained in the same package containing a first formulation containing the compound of the present invention and a second formulation containing one or more further compounds, thereby the formulation types may be the same or different.

[0679] It is within the scope of the present invention that more than one form of the compound of the present invention may be contained in the composition of the present invention and / or the pharmaceutical composition of the present invention. It is also within the scope of the present invention that more than one form of the compound of the present invention may be used, preferably administered, in the method of the present invention.

[0680] It will be recognized that the compositions of the present invention and the pharmaceutical compositions of the present invention can be manufactured in the conventional manner. Radiopharmaceuticals have radioactivity that decreases over time as a result of radioactive decay. The physical half-life of radionuclides is often short for radiopharmaceutical diagnostics. In these cases, final preparation must be performed immediately before administration to the patient. This is especially true for positron-emitting radiopharmaceuticals (PET radiopharmaceuticals) for tomography. This often results in the use of semi-finished products such as radionuclide generators, radioprotozoa, and kits.

[0681] Preferably, the kit of the present invention, apart from one or more compounds of the present invention, typically includes: instructions for use, a final preparation and / or a quality control, one or more optional excipients, one or more optional reagents for a labeling procedure, one or more radionuclides, optionally including or not including a shielding container, and optionally at least one of one or more devices, the device being selected from the group including labeling devices, purification devices, analytical devices, handling devices, radiation protection devices, or administration devices.

[0682] Shielding containers known as "pig iron" containers, used for the general handling and transport of radiopharmaceutical containers, come in various configurations for holding radiopharmaceutical containers such as bottles, vials, and syringes. One form often includes a removable cover that allows access to the held radiopharmaceutical solution. Radiation exposure is acceptable when the pig iron cover is in place.

[0683] Labeling devices are selected from a group including open reactors, closed reactors, microfluidic systems, nanoreactors, cartridges, pressure vessels, vials, temperature-controllable reactors, mixing or shaking reactors, and combinations thereof.

[0684] The purification device is preferably an ion exchange chromatography column or device. The group is selected from size exclusion chromatography columns or devices, affinity chromatography columns or devices, gas or liquid chromatography columns or devices, solid-phase extraction columns or devices, filtration devices, and centrifugation vial columns or devices.

[0685] The analytical device is preferably selected from a group of testing devices for determining identity, radiochemical purity, radionuclide purity, radioactive content, and specific radioactivity of radiolabeled compounds.

[0686] The handling device is preferably selected from the group consisting of devices for mixing, diluting, dispensing, labeling, injecting, and administering radiopharmaceuticals to a target. Radiation protection devices are used to protect physicians and other individuals from radiation when using therapeutic or diagnostic radionuclides. Preferably, radiation protection devices are selected from the group consisting of devices having a protective barrier of radiation-absorbing material selected from the group consisting of aluminum, plastic, wood, lead, iron, lead glass, water, rubber, plastic, and cloth; devices that ensure sufficient distance from radiation sources; devices that reduce exposure time to radionuclides; devices that limit inhalation, ingestion, or other modes of entry of radioactive materials into the body; and devices that provide combinations of these means.

[0687] The administration device is preferably selected from the group of syringes, protective syringes, needles, pumps, and infusion devices. Syringe protection is generally a hollow cylindrical structure that houses the cylindrical body of the syringe and is made of lead or tungsten, including a lead glass window that allows the handler to see the syringe plunger and the liquid volume inside the syringe.

[0688] The present invention will now be further described with reference to the following drawings and examples, from which further features, embodiments, and advantages can be obtained. [Brief explanation of the drawing]

[0689] [Figure 1] Figure 1 shows the radiochromatogram of 177Lu-3BP-3407 in a formulation buffer containing 100 mg / mL ascorbate and 5 mg / mL L-methionine, analyzed immediately after synthesis. [Figure 2] Figure 2 shows the radiochromatogram of 177Lu-3BP-3407 in a formulation buffer containing 100 mg / mL ascorbate and 5 mg / mL L-methionine, analyzed 6 days after synthesis. [Figure 3] Figure 3 shows the radiochromatogram of 177Lu-3BP-3554 in a formulation buffer containing 100 mg / mL ascorbate and 5 mg / mL L-methionine, analyzed immediately after synthesis. [Figure 4] Figure 4 shows the radiochromatogram of 177Lu-3BP-3554 in a formulation buffer containing 100 mg / mL ascorbate and 5 mg / mL L-methionine, analyzed 6 days after synthesis. [Figure 5] Figure 5 shows the percentage of injected dose per gram of tissue (%ID / g) uptake of 111In-3BP-3105(A) and 111In-3BP-3168(B) in the kidney, liver, blood pool, and HEK-FAP tumors, as determined by SPECT imaging at 1, 3, 6, and 24 hours after injection into a mouse model. [Figure 6] Figure 6 shows the percentage of injected dose per gram of tissue (%ID / g) uptake of 111In-3BP-3320(A) and 111In-3BP-3321(B) in the kidney, liver, blood pool, and HEK-FAP tumors, as determined by SPECT imaging at 1, 3, 6, and 24 hours after injection into a mouse model. [Figure 7]Figure 7 shows the percentage of injected dose per gram of tissue (%ID / g) uptake of 111In-3BP-3275(A) and 111In-3BP-3397(B) in the kidney, liver, blood pool, and HEK-FAP tumors, as determined by SPECT imaging at 1, 3, 6, and 24 hours after injection into a mouse model. [Figure 8] Figure 8 shows the percentage of injected dose per gram of tissue (%ID / g) uptake of 111In-3BP-3398(A) and 111In-3BP-3407(B) in the kidney, liver, blood pool, and HEK-FAP tumors, as determined by SPECT imaging at 1, 3, 6, and 24 hours after injection into a mouse model. [Figure 9] Figure 9 shows the percentage of injected dose per gram of tissue (%ID / g) uptake of 111In-3BP-3554(A) and 111In-3BP-3652(B) in the kidney, liver, blood pool, and HEK-FAP tumors, as determined by SPECT imaging at 1, 3, 6, and 24 hours after injection into a mouse model. [Figure 10] Figure 10 shows the percentage of injected dose per gram of tissue (%ID / g) uptake of 111In-3BP-3654(A) and 111In-3BP-3656(B) in the kidney, liver, blood pool, and HEK-FAP tumors, as determined by SPECT imaging at 1, 3, 6, and 24 hours after injection into a mouse model. [Figure 11] Figure 11 shows the percentage of injected dose per gram of tissue (%ID / g) uptake of 111In-3BP-3659(A) and 111In-3BP-3678(B) in the kidney, liver, blood pool, and HEK-FAP tumors, as determined by SPECT imaging at 1, 3, 6, and 24 hours after injection into a mouse model. [Figure 12]Figure 12 shows the percentage of injected dose per gram of tissue (%ID / g) uptake of 111In-3BP-3692(A) and 111In-3BP-3767(B) in the kidney, liver, blood pool, and HEK-FAP tumors, as determined by SPECT imaging at 1, 3, 6, and 24 hours after injection into a mouse model. [Figure 13] Figure 13 shows SPECT images of 111In-3BP-3554 at 1, 3, 6, 24, and 48 hours after injection into mice with HEK-FAP tumors. [Figure 14] Figure 14 shows SPECT images of 111In-3BP-3767 at 1, 3, 6, 24, and 48 hours after injection into mice with HEK-FAP tumors. [Figure 15A] Figure 15A shows the time course of tumor growth in mice with HEKFAP tumors treated with the vehicle, the cold compound natLu-3BP-3554, 30 MBq (low dose) 177Lu-3BP-3554, and 60 MBq (high dose) 177Lu-3BP-3554. [Figure 15B] Figure 15B shows the percentage change in body weight over time in mice with HEK-FAP tumors treated with the vehicle, the cold compound natLu-3BP-3554, 30 MBq (low dose) 177Lu-3BP-3554, and 60 MBq (high dose) 177Lu-3BP-3554. [Figure 16A] Figure 16A shows representative SPECT / CT images over time of the in vivo distribution of 60 MBq 177 Lu-3BP-3554 in mice with HEK-FAP tumors. [Figure 16B] Figure 16B shows representative SPECT / CT images over time of the in vivo distribution of 30 MBq 177Lu-3BP-3554 in mice with HEK-FAP tumors. [Figure 17A] Figure 17A shows representative SPECT / CT images of four different sarcoma PDX models 3 hours after administration of 111In-3BP-3554. [Figure 17B]Figure 17B shows the %ID / g uptake of 111In-3BP-3554 in four different sarcoma PDX models 3 hours after injection. [Figure 18A] Figure 18A shows the time course of tumor growth in mice with Sarc4809 PDX tumors treated with the vehicle, the cold compound natLu-3BP-3554, 30 MBq 177Lu-3BP-3554, or 60 MBq 177Lu-3BP-3554. [Figure 18B] Figure 18B shows the time course of body weight changes in mice with sarcoma Sarc4809 PDX tumors treated with vehicle, the cold compound natLu-3BP-3554, 30 MBq 177Lu-3BP-3554, or 60 MBq 177Lu-3BP-3554. [Figure 19] Figure 19 shows the amino acid sequences of human fibroblast-activating protein (FAP) (SEQ ID NO: 1), human dipeptidyl peptidase 4 (DPP4) (SEQ ID NO: 2), and human prolyl endopeptidase (PREP) (SEQ ID NO: 3).

[0690] The following examples are included to provide guidance to those skilled in the art for carrying out typical embodiments of the subject matter of this disclosure. Given the general level of skill in this disclosure and the art, those skilled in the art will understand that the following examples are intended to be illustrative only, and that numerous variations, modifications, and changes may be adopted without departing from the scope of the subject matter of this disclosure. The following descriptions of synthesis and specific examples are intended for illustrative purposes only and should not be construed as limiting in any way the compounds of this disclosure may be prepared by any other means. [Examples]

[0691] The abbreviations used in this application and in particular in the following embodiments are as follows: 4PL stands for 4-parameter logistic curve fitting. Å stands for angstrom.

[0692] ACN stands for acetonitrile. Ahx stands for 6-aminohexanoic acid. AMC stands for 7-amino-4-methylcoumarin.

[0693] amu stands for atomic mass unit. aq. means water-based. AUC inf This represents the area under an infinitely extrapolated curve.

[0694] BSA stands for bovine serum albumin. C0 represents the initial concentration of the compound. CAF stands for cancer-associated fibroblasts.

[0695] CL stands for clearance. CM stands for ChemMatrix (trademark). CT stands for Computed Tomography.

[0696] Cy5 stands for cyanine-5. DAD stands for Diode Array Detector. DCM stands for dichloromethane.

[0697] Dde is N-(1-(4,4-dimethyl-2,6-dioxocyclohexylidene) It means (chill). DEG stands for diethylene glycol dimethacrylate.

[0698] DIC stands for N,N'-diisopropylcarbodiimide. DICOM stands for Digital Imaging and Communication in Pharmaceuticals.

[0699] DIPEA stands for diisopropylethylamine. DMF stands for N,N-dimethylformamide. DMSO stands for dimethyl sulfoxide.

[0700] DOTA stands for 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid. DOTA(tBu)3-OH stands for tri-tert-butyl-1,4,7,10-tetraazacyclo-dodecane-1,4,7,10-tetraacetate.

[0701] DPP stands for dipeptidyl peptidase. EC stands for Electron Capture. EC 50 This represents half of the maximum excitation concentration.

[0702] ECACC stands for European Collection of Authenticated Cell Cultures. EDC stands for 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide.

[0703] EMEM stands for Eagle Minimum Essential Medium. eq or eq. means equivalent. ESI stands for electrospray ionization.

[0704] Et2O stands for diethyl ether. RINKAN stands for ethyl acetate. FACS stands for Fluorescence Activated Cell Sorting.

[0705] FAP stands for fibroblast-activating protein. Fb stands for background fluorescence intensity. FBS stands for fetal bovine serum.

[0706] FGF21 stands for fibroblast growth factor 21. FITC stands for 5(6)-fluorescein isothiocyanate. Fmoc stands for 9-fluorenylmethoxycarbonyl.

[0707] FRET stands for Fluorescence Resonance Energy Transfer. Ft represents fluorescence intensity. Gab stands for gamma-aminobutyric acid.

[0708] GABA stands for gamma-aminobutyric acid. 'h' stands for time. HATU stands for O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate.

[0709] HBST stands for SPR Running Buffer. HEK-FAP refers to human embryonic kidney 293 cells that express human FAP. HEPES stands for 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid.

[0710] HFIP stands for hexafluoro-2-isopanol. HOAc means acetic acid. HOAt stands for 1-hydroxy-7-azabenzotriazole.

[0711] HPLC stands for High-Performance Liquid Chromatography. HPLC / MS stands for High-Performance Liquid Chromatography / Mass Analysis. I C 50 This represents half the maximum inhibitory concentration.

[0712] ID / g refers to the injected dose per gram. IS stands for nuclear isomer transition. iTLC-SG stands for Instant Thin-Layer Chromatography-Silica Gel.

[0713] K2EDTA stands for dipotassium ethylenediaminetetraacetate. K D This represents the dissociation constant. kDa stands for 1000 Daltons.

[0714] K i This represents the inhibition constant. k off This refers to the dissociation rate. k on This refers to the speed of meeting.

[0715] LC / TOF-MS stands for Liquid Chromatography / Time of Flight / Mass Spectrometry. LC-MS stands for High-Performance Liquid Chromatography with Mass Spectrometry. LDH stands for lactate dehydrogenase.

[0716] Leu means leucine. LiOH stands for lithium hydroxide. M stands for molar concentration or moles per liter.

[0717] m / z represents mass divided by electric charge. "max." means maximum. MeOH stands for methanol.

[0718] MeV stands for megaelectronvolt. "Min" means minutes. MMP stands for matrix metalloproteinase.

[0719] MRM stands for Multiple Reaction Monitoring. MTBE stands for methyl-tert-butyl ether. Mtt stands for methyltrityl.

[0720] MTV stands for Mean Tumor Volume. MW stands for molecular weight. "nd" means undecided.

[0721] Na2SO4 means sodium sulfate. NaCl stands for sodium chloride. NaHCO3 stands for sodium bicarbonate.

[0722] NCA stands for Non-Compartmental Analysis. NHS stands for N-hydroxysuccinimide. NMP stands for 1-methyl-2-pyrrolidone.

[0723] NOS stands for Unidentifiable. Oic stands for L-octahydroindole-2-carboxylic acid. PA stands for "for analytical purposes" (quality grade).

[0724] "pi" means after injection. Pbf stands for 2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-sulfonyl.

[0725] PBS stands for phosphate-buffered saline. PDX stands for patient-derived xenograft. PET stands for Positron Emission Tomography.

[0726] pIC50 represents the negative logarithm of the IC50 value when converted to molar concentration. POP stands for prolyl oligopeptidase. ppm means one part per million.

[0727] PREP stands for prolyl endopeptidase. "Prep." means to allocate or portion. PS stands for polystyrene.

[0728] Q-TOF stands for Quadrupole Flight Time. Ref means reference. RFU stands for Relative Fluorescence Unit.

[0729] RLB stands for Radioligand Binding Assay. RMCE stands for Recombinase-mediated Cassette Exchange. RP stands for reverse phase.

[0730] R t This refers to the holding time. RT stands for room temperature. RU stands for Resonance Unit.

[0731] SAR stands for structure-activity relationship. sat. means saturation. SCID stands for Severe Combined Immunodeficiency.

[0732] SCK stands for Single Cycle Kinetics. sec or s means seconds. SF stands for spontaneous nuclear fission.

[0733] SPECT stands for Single-Photon Emission Computed Tomography. SPPS stands for Solid-Phase Peptide Synthesis. t 1 / 2 This refers to the terminal half-life.

[0734] tBu stands for tert.butyl. TFA stands for trifluoroacetate or trifluoroacetic acid. TG stands for TentaGel.

[0735] TGI stands for Tumor Growth Inhibition. THF stands for tetrahydrofuran. TIPS stands for triisopropylsilane.

[0736] TLC stands for Thin-Layer Chromatography. TME stands for Tumor Microenvironment. t RThis refers to the holding time.

[0737] UHPLC stands for ultra-high-performance liquid chromatography. UV stands for ultraviolet light. V ss This refers to the volume of distribution in a steady state.

[0738] V Z This represents the volume of distribution in the final phase. Example 1 material and method Materials and methods, as well as general methods, will be further explained by the following examples.

[0739] solvent: The solvent was used at the specified quality without further purification. Acetonitrile (Super Gradient, HPLC, VWR - for analytical purposes; PrepSolv, Merck - for preparative purposes); Dichloromethane (synthetic, Roth); Ethyl acetate (synthetic grade, Roth); N,N-dimethylformamide (peptide synthesis grade, Biosolve); 1-Methyl-2-pyrrolidone (peptide grade, IRIS BioTech); 1,4-dioxane (reinst, Roth); Methanol (pa, Merck).

[0740] Water: Milli-Q Plus, Millipore, desalted. Chemicals: The chemical substances were synthesized according to the literature procedure, or synthesized in a manner similar to the literature procedure, or were sourced from Sigma-Aldrich-Merck (Deisenhofen, Germany), Bachem (Bubendorf, Switzerland), VWR (Darmstadt, Germany), Novabiochem (Merck Group, Darmstadt, Germany), Acros Organics (distributed by Fisher Scientific GmbH, Schwerte, Germany), Iris Biotech (Marktredwitz, Germany), Amatek Chemical (Jiangsu, China), Roth (Karlsruhe, Germany), Molecular Devices (Chicago, USA), Biochrom (Berlin, Germany), Peptech (Cambridge, MA, USA), Synthetech (Albany, OR, USA), Pharmacore (High Point, NC, USA), PCAS Biomatrix We purchased and used the specified quality without further purification from companies such as Inc (Saint-Jean-sur-Richelieu, Quebec, Canada), Alfa Aesar (Karlsruhe, Germany), Tianjin Nankai Hecheng S&T Co., Ltd (Tianjin, China), CheMatech (Dijon, France), and Anaspec (San Jose, CA, USA), or other companies.

[0741] Boc4N4Ac-OH was synthesized according to the procedure described in the literature (Maecke et al. Chem.Eur.J., 2010, 16, 7, 2115).

[0742] [ka]

[0743] cell: HT29 (ECACC catalog number 91072201) and WI-38 (ECACC catalog number 90020107) were purchased from ECACC, and HEK293 cells (Q12884) expressing human FAP were prepared by InSCREENeX GmbH (Braunschweig, Germany) using recombinase-mediated cassette exchange (RMCE). The RMCE procedure is described by Nehlsen et al. (Nehlsen, et al., BMC Biotechnol, 2009, 9:100). HPLC / MS analysis HPLC / MS analysis was performed by injecting 5 μl of sample solution and using a two-step gradient (5 to 65% B at 12 min, followed by 65 to 90% at 0.5 min, A: 0.1% TFA in water, and B: 0.1% TFA in ACN) for all chromatograms. The RP column was manufactured by Agilent (Type Poroshell 120, 2.7 μm, EC-C18, 50 × 3.00 mm, flow rate 0.8 ml, HPLC at room temperature); mass spectrometer: Agilent 6230 LC / 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 The time is expressed in decimal (e.g., 1.9 minutes = 1 minute 54 seconds) and refers to detection by UV spectrometer. For evaluation of the mass of the observed compound, see "Find Compounds by The "Formula" function was used. Specifically, the identity of the compounds was confirmed using the "neutral mass (in Daltons)" value of each compound and the corresponding isotope distribution pattern. The accuracy of the mass spectrometer was approximately ±5 ppm.

[0744] Preparative HPLC: Preparative HPLC separation was performed using a reversed-phase column (Phenomenex Kinetex 5μ XB-C18 100Å, 150×30mm, or RLRP-S 8μ, 100Å, 150×25mm) as the stationary phase. 0.1% TFA(A) in water and 0.1% TFA(B) in ACN were used as the mobile phase, mixed in a linear binary gradient. This gradient was described as "10 to 40% in 30 minutes," meaning a linear gradient from 10%B (and corresponding 90%A) to 40%B (and corresponding 60%A) was performed within 30 minutes. The flow rate was in the range of 30–50 ml / min. A typical gradient for the purification of the compounds of the present invention started at 5–25%B and ended at 30–50%B after 30 minutes, with a difference of at least 10% in the percentage of B between the end and start. The commonly used gradient was "15 to 40% B in 30 minutes".

[0745] General procedures for automated / semi-automated solid-phase synthesis: Automated solid-phase synthesis of peptides and polyamides was performed on 50 μmol and 100 μmol scales using a Tetras Peptide Synthesizer (Advanced ChemTech). Manual processes were performed in plastic syringes with frit (material: PE, Roland Vetter Laborbedarf OHG, Ammerbuch, Germany). Reagent quantities in the described protocols correspond to the 100 μmol scale unless otherwise specified.

[0746] Solid-phase synthesis was carried out using polystyrene resin (crosslinked with 1,4-divinylbenzene (PS) or di(ethylene glycol) dimethacrylate (DEG)), ChemMatrix (CM) resin, or TentaGel (TG) resin. The resin linkers were trityl, wang, and linkamide.

[0747] Resin filling: In the case of trityl linker, the attachment (resin filling) of the first building block was carried out as follows: The resin (polystyrene (PS) trityl chloride, initial filling amount: 1.8 mmol / g) was swollen in DCM (5 ml) for 30 minutes, followed by washing with DCM (3 ml, 1 min). Next, this resin was treated for 1 hour with a mixture of the corresponding building block (0.5 mmol, 5 eq.) and DIPEA (350 μl, 3.5 mmol, 35 eq.) in DCM (4 ml). After that, the resin was washed with methanol (5 ml, 5 min) and DMF (3 ml, twice × 1 min).

[0748] In the case of Wang linkers, pre-filled resins (polystyrene (PS) and TentaGel (TG)) were used. In the case of the link amide linker, the attachment of the first residue to the resin (CM, DEG) was carried out using the same procedure as in the chain construction described below.

[0749] Alloc / Allele Deprotection: After swelling in DMF, the resin was washed with DMF and DCM. The DCM was deoxygenated by passing a stream of nitrogen through the stirred solvent. The resin was washed twice (trice) with an oxygen-free solvent. Next, 2 ml of a 2 M solution of barbituric acid in oxygen-free DCM and 1 ml of a 25 μM solution of tetrakis(triphenylphosphine)palladium(0) in oxygen-free DCM were added to the resin. The resin was stirred for 1 hour, and then washed with DCM, MeOH, DMF, 5% DIPEA in DMF, 5% dithiocarbamate in DMF, DMF, and DCM (each washing step was repeated three times at 3 ml for 1 minute).

[0750] Fmoc deprotection: After swelling in DMF, the resin was washed with DMF, then treated with piperidine / DMF (1:4, 3 ml, 2 and 20 minutes), followed by washing with DMF (3 ml, 5 times x 1 minute).

[0751] Dde deprotection: After swelling in DMF, the resin was washed with DMF, then treated with hydrazine hydrate / DMF (2 / 98, 3 ml, twice for 10 minutes), and subsequently washed with DMF (3 ml, five times for 1 minute).

[0752] Mtt deprotection: After swelling in DCM, the resin was washed with DCM, then treated with HFIP / DCM (7 / 3, 4-6 ml, 4 hours), followed by washing with DCM (3 ml, 3 times x 1 min), DMF (3 ml, 3 times x 1 ml), and DIPEA (0.9 M in DMF, 3 ml, 1 min).

[0753] Reagent soluti...

Claims

1. Equation (I) 【Chemistry 1】 cyclic peptide and a compound comprising an N-terminal modification group A bonded to Xaa1, The peptide sequence is drawn from left to right in the direction from the N-terminus to the C-terminus. Xaa1 is equation (II) 【Chemistry 2】 It is a residue of the amino acid, R １ａ is -NH-, R １ｂ is H or CH ３ And, n = 0 or 1, The N-terminal modification group A is covalently bonded to the nitrogen atom of Xaa1, The carbonyl group of Xaa1 is covalently bonded to the nitrogen of Xaa2. The sulfur atom of Xaa1 is covalently bonded to Yc as a thioether. Xaa2 is equation (III), (IV), or (XX) 【Transformation 3】 It is a residue of the amino acid, R ２ａ , R ２ｂ , R ２ｃ are each independently selected from the group consisting of (C １ - C ２ ), alkyl and H, and the (C １ - C ２ ) alkyl may be substituted by a substituent selected from the group consisting of OH, NH ２ , halogen, (C ５ - C ７ ) cycloalkyl, p = 0, 1, or 2, v = 1 or 2, w = 1, 2, or 3, The amino acid in formula (IV) has methyl, OH, and NH at positions 3 and 4 of the indicated ring. ２ , and may be substituted with one or two substituents selected from the group consisting of F, Xaa3 is expression (V) or (XX) 【Chemistry 4】 It is a residue of the amino acid, X ３ CH ２ CF ２ CH-R ３ｂ Selected from the group consisting of S, O, and NH, p = 1 or 2, v = 1 or 2, w = 1, 2, or 3, R ３ａ H, methyl, OH, NH ２ , or F, R ３ｂ methyl, OH, NH ２ , or F, Xaa4 is equation (VI) 【Transformation 5】 It is a residue of the amino acid, R ４ａ H, OH, COOH, CONH ２ , X ４ , and -NH-CO-X ４ Selected from the group consisting of X ４ But (C １ ~C ６ ) alkyl, (C ５ ~C ６ ) Aryl, and (C ５ ~C ６ ) Selected from the group consisting of heteroaryls, X ４ methyl, CONH ２ , halogen, NH ２ They may be substituted with one or two substituents selected from the group consisting of , and OH. q = 1, 2, or 3, and the one, two, or three CH ２ - One or two hydrogen atoms of the group are individually methyl, ethyl, or (C) as needed. ５ ~C ６ )aryl, or (C ５ ~C ６ ) Substituted by heteroaryl, R ４ｂ is methyl or H, Xaa5 is structure (VII) 【Transformation 6】 It is a residue of the amino acid, R ５ OH and NH ２ Selected from the group, r = 1, 2, or 3, Xaa6 is an amino acid selected from the group consisting of aromatic L-α-amino acids and heteroaromatic L-α-amino acids. Xaa7 is equation (IX) 【Transformation 7】 It is an aminothiol or amino acid residue, R ７ａ -CO-, -COOH, -CONH ２ ien-CH ２ -OH, -(CO)-NH-R ７ｂ , -(CO)-(NR ７ｃ )-R ７ｂ , or H, R ７ｂ and R ７ｃ Each independently (C １ ~C ４ ) is alkyl, t is 1 or 2, Yc is equation (X) 【Transformation 8】 The structure is such that the sulfur atom of Xaa1 and the sulfur atom of Xaa7 are linked under the formation of two thioether linkages, thereby forming formula (XXI) 【Chemistry 9】 It forms a ring structure, The substitution pattern of the aromatic group in formula (X) is ortho, meta, or para. n = 0 or 1, t = 1 or 2, Y １ is C-H or N, Y ２ is N or CR ｃ１ And, R ｃ１ is H or CH ２ -R ｃ２ And, R ｃ２ is equation (XI), (XII), or (XXII) 【Chemistry 10】 It has the structure of, R ｃ３ and R ｃ４ H and (C) are independent of each other. １ ~C ４ ) Selected from the group consisting of alkyl, u = 1, 2, 3, 4, 5, or 6, x and y are independently 1, 2, or 3, X = O or S, In equations (XI) and (XXII), one of the nitrogen atoms is R ｃ１ of -CH ２ It is connected to -, and in equation (XII), -X- is R ｃ１ of -CH ２ - is connected, The N-terminal modification group A is a blocking group Abl or an amino acid Aaa. compound.

2. Equation (I) 【Chemistry 11】 cyclic peptide and a compound comprising an N-terminal modification group A bonded to Xaa1, The peptide sequence is drawn from left to right in the direction from the N-terminus to the C-terminus. Xaa1 is equation (II) 【Chemistry 12】 It is a residue of the amino acid, R １ａ is -NH-, R １ｂ is H or CH ３ And, n = 0 or 1, The N-terminal modification group A is covalently bonded to the nitrogen atom of Xaa1, The carbonyl group of Xaa1 is covalently bonded to the nitrogen of Xaa2. The sulfur atom of Xaa1 is covalently bonded to Yc as a thioether. Xaa2 is equation (III), (IV), or (XX) 【Chemistry 13】 It is a residue of the amino acid, R ２ａ , R ２ｂ , R ２ｃ Each independently (C １ ~C ２ ) Selected from the group consisting of alkyl and H, and the (C １ ~C ２ ) Alkyl is OH, NH ２ , halogen, (C ５ ~C ７ ) They may be substituted with substituents selected from the group consisting of cycloalkyl groups, p = 0, 1, or 2, v = 1 or 2, w = 1, 2, or 3, The amino acid in formula (IV) has methyl, OH, and NH at positions 3 and 4 of the indicated ring. ２ , and may be substituted with one or two substituents selected from the group consisting of F, Xaa3 is expression (V) or (XX) 【Chemistry 14】 It is a residue of the amino acid, X ３ CH ２ CF ２ CH-R ３ｂ Selected from the group consisting of S, O, and NH 、 p = 1 or 2, v = 1 or 2, w = 1, 2, or 3, R ３ａ H, methyl, OH, NH ２ , or F, R ３ｂ is methyl, OH, NH ２ , or F, and Xaa4 is equation (VI) 【Chemistry 15】 It is a residue of the amino acid, R ４ａ is selected from the group consisting of H, OH, COOH, CONH ２ , X ４ , and -NH-CO-X ４ ; X ４ is selected from the group consisting of (C １ ~C ６ )alkyl, (C ５ ~C ６ )aryl, and (C ５ ~C ６ )heteroaryl; X ４ may be substituted by one or two substituents selected from the group consisting of methyl, CONH ２ , halogen, NH ２ , and OH, q = 1, 2, or 3, and the one, two, or three CH ２ - One or two hydrogen atoms of the group are individually methyl, ethyl, or (C) as needed. ５ ~C ６ )aryl, or (C ５ ~C ６ ) Substituted by heteroaryl, R ４ｂ is methyl or H, Xaa5 is structure (VII) 【Chemistry 16】 It is a residue of the amino acid, R ５ OH and NH ２ Selected from the group, r = 1, 2, or 3, Xaa6 is an amino acid selected from the group consisting of aromatic L-α-amino acids and heteroaromatic L-α-amino acids. Xaa7 is equation (IX) 【Chemistry 17】 It is an aminothiol or amino acid residue, R ７ａ -CO-XXX, -COOH, -CONH ２ ien-CH ２ -OH, -(CO)-NH-R ７ｂ , -(CO)-(NR ７ｃ )-R ７ｂ , or H, where XXX is an amino acid or peptide that forms an amide bond with the carbonyl carbon atom, R ７ｂ and R ７ｃ Each independently (C １ ~C ４ ) is alkyl, The aforementioned amino acids or peptides are optionally substituted with Z groups. t is 1 or 2, Yc is equation (X) [Chemistry 18] The structure is such that the sulfur atom of Xaa1 and the sulfur atom of Xaa7 are linked under the formation of two thioether linkages, thereby forming formula (XXI) 【Chemistry 19】 It forms a ring structure, The substitution pattern of the aromatic group in formula (X) is ortho, meta, or para. n = 0 or 1, t = 1 or 2, Y １ is C-H or N, Y ２ is N or CR ｃ１ And, R ｃ１ is H or CH ２ -R ｃ２ And, R ｃ２ is equation (XI), (XII), or (XXII) 【Chemistry 20】 It has the structure of, R ｃ３ and R ｃ４ H and (C) are independent of each other. １ ~C ４ ) Selected from the group consisting of alkyl, R ｃ５ is an H or Z group, u = 1, 2, 3, 4, 5, or 6, x and y are independently 1, 2, or 3, X = O or S, In equations (XI) and (XXII), one of the nitrogen atoms is R ｃ１ of -CH ２ It is connected to -, and in equation (XII), -X- is R ｃ１ of -CH ２ - is connected, The N-terminal modification group A is a blocking group Abl or an amino acid Aaa, and the amino acid Aaa may be substituted with a Z group as needed, and each Z group contains a chelator and, optionally, a linker. compound.

3. R ｃ５ However, it is a Z group that includes a chelator and, if necessary, a linker. R ７ａ -CO-XXX, -COOH, -CONH ２ ien-CH ２ -OH, -(CO)-NH-R ７ｂ , -(CO)-(NR ７ｃ )-R ７ｂ , or H, R ７ｂ and R ７ｃ Each independently (C １ ~C ４ ) is an alkyl group, where XXX is an amino acid or peptide that forms an amide bond with the carbonyl carbon atom, and the amino acid or peptide is Z Not substituted by the group, If the N-terminal modification group A is an amino acid Aaa, then the amino acid Aaa is not substituted with a Z group including a chelator and, optionally, a linker. The compound according to claim 2.

4. R ７ａ Unlike -CO-XXX, XXX is an amino acid or peptide that forms an amide bond with the carbonyl carbon atom. If the N-terminal modification group A is an amino acid Aaa, then the amino acid Aaa is not substituted with a Z group including a chelator and, optionally, a linker. The compound according to any one of claims 2 and 3.

5. R ７ａ is -CO-XXX, where XXX is an amino acid or peptide that forms an amide bond with the carbonyl carbon atom, and the amino acid or peptide is substituted with a Z group containing a chelator and optionally a linker. R ｃ１ or R ｃ５ H is, If the N-terminal modification group A is an amino acid Aaa, then the amino acid Aaa is not substituted with a Z group including a chelator and, optionally, a linker. The compound according to claim 2.

6. The N-terminal modification group A is an amino acid Aaa substituted with a Z group containing a chelator and, optionally, a linker. R ｃ１ or R ｃ５ H is, R ７ａ ga-CO-XXX-COOH,-CONH ２ ien-CH ２ -OH, -(CO)-NH-R ７ｂ , -(CO)-(NR ７ｃ )-R ７ｂ , or H, R ７ｂ and R ７ｃ Each independently (C １ ~C ４ ) is alkyl, where XXX is an amino acid or peptide that forms an amide bond with the carbonyl carbon atom, and the amino acid or peptide is not substituted with a Z group including a chelator and optionally a linker. The compound according to claim 2.

7. R ７ａ The compound according to claim 6, wherein, unlike -CO-XXX, XXX is an amino acid or peptide that forms an amide bond with the carbonyl carbon atom.

8. The amino acids Aaa each have structure (XIV) 【Chemistry 21】 It is a D-amino acid residue or an L-amino acid residue, R ａ２ But (C １ ~C ６ ) alkyl, modified (C １ ~C ６ ) alkyl, (C １ ~C ３ ) alkyl, modified (C １ ~C ３ ), (C ３ ~C ８ ) Carbocycle, aryl, heteroaryl, and (C ３ ~C ８ ) Selected from a group consisting of complex algebras, Modified (C １ ~C ６ ) One -CH in the alkyl group ２ - The group is replaced by -S- or -O- and modified (C １ ~C ３ ) In the alkyl group, one of the H atoms is substituted with OH, F, or COOH, or two of the H atoms are substituted with F, R ａ３ This is the Z group. The compound according to any one of claims 2, 6, and 7.

9. The blocking group Abl is R ａ１ -C(O)-, R ａ１ -S(O ２ ) -, R ａ１ -NH-C(O)-, and R ａ１ Selected from the group consisting of -O-C(O)-, R ａ１ Required Independently, OH, F, COOH, (C ３ ~C ８ ) Cycloalkyl, aryl, heteroaryl, and (C ３ ~C ８ ) Substituted by up to two substituents selected from the group consisting of heterocycles (C １ ~C ８ ) is alkyl, (C １ ~C ８ ) in alkyl groups -CH ２ The compound according to any one of claims 1 to 5, wherein one of the groups is replaced by -S- or -O- as necessary.

10. The compound according to claim 9, wherein the blocking group Abl is hexanoyl or pentylsulfonyl, preferably the blocking group Abl is hexanoyl.

11. The amino acids Aaa each have structure (XIV) 【Chemistry 22】 It is a D-amino acid residue or an L-amino acid residue, R ａ２ But (C １ ~C ６ ) alkyl, modified (C １ ~C ６ ) alkyl, (C １ ~C ３ ) alkyl, modified (C １ ~C ３ ), (C ３ ~C ８ ) Carbocycle, aryl, heteroaryl, and (C ３ ~C ８ ) Selected from a group consisting of complex algebras, Modified (C １ ~C ６ ) One -CH in the alkyl group ２ - The group is replaced by -S- or -O- and modified (C １ ~C ３ ) In the alkyl group, one of the H atoms is substituted with OH, F, or COOH, or two of the H atoms are substituted with F, R ａ３ is H or acetyl, The compound according to any one of claims 1 to 5.

12. The compound according to any one of claims 1 to 11, wherein the amino acid Aaa is selected from the group consisting of amino acid residues of Nle, nle, Met, and met, and their derivatives.

13. The compound according to any one of claims 1 to 12, wherein Xaa1 is a D-amino acid residue selected from the group consisting of cys, hcy, and pen, or Xaa1 is an L-amino acid residue selected from the group consisting of Cys, Hcy, and Pen.

14. Xaa2 is an amino acid residue selected from the group consisting of Pro, Gly, Nmg, and their derivatives; Xaa3 is an amino acid residue selected from the group consisting of Pro, Hyp, Tfp, Cfp, Dmp, Aze, and Pip, and their derivatives; Xaa4 is an amino acid residue selected from the group consisting of Thr, Hse, Asn, Gln, and Ser, and their derivatives; Xaa5 is an amino acid residue selected from the group consisting of Gln and Glu, and their derivatives; and Xaa6 is an amino acid residue of formula (VIIIIa), (VIIIIb), (VIIIIc), and (VIIIId) 【Chemistry 23】 It is any one of the amino acid residues, R ６ａ and R ６ｂ Each of these is independently selected from the group consisting of H, methyl, ethyl, propyl, and isopropyl. R ６ｃ The ∫ represents 0 to 3 substituents, and each substituent independently represents Cl, F, Br, NO ２ NH ２ ,CN,CF ３ OH, OR ６ｄ , and C １ ~C ４ Selected from the group consisting of alkyl groups, R ６ｄ is selected from the group consisting of methyl, ethyl, propyl, and isopropyl, s is 0 or 1, Preferably Xaa6 is formula (VIIIa), (VIIIb), (VIIIc), and (VIIId) 【Chemistry 24】 It is any one of the amino acid residues, R ６ａ and R ６ｂ These are H, R ６ｃ The ∫ represents 0 to 2 substituents, and each substituent independently represents Cl, F, Br, NO ２ NH ２ ,CN,CF ３ OH, OR ６ｄ Selected from the group consisting of , and methyl, R ６ｄ is selected from the group consisting of methyl, ethyl, propyl, and isopropyl, s is 0, and / or Xaa7 is an aminothiol residue selected from the group consisting of Cys, Cysol, AET, Hcy, cys, and hcy. The compound according to any one of claims 1 to 13.

15. Xaa2 is an amino acid residue selected from the group consisting of Pro, Gly, and Nmg; Xaa3 is an amino acid residue selected from the group consisting of Pro and Hyp; Xaa4 is an amino acid residue Thr; Xaa5 is an amino acid residue selected from the group consisting of Gln and Glu; Xaa6 is an amino acid residue selected from the group consisting of Phe, 1Ni, Mpa, Otf, and Thi; and Xaa7 is an aminothiol residue selected from the group consisting of Cys, Cysol, and AET. The compound according to any one of claims 1 to 14.

16. Formula (LI), (LII), (LIII), or (LIV) 【Chemistry 25】 A compound according to any one of claims 1 and 9 to 15, which is a compound of the above.

17. Formula (LI), (LII), (LIII), or (LIV) 【Chemistry 26】 A compound according to any one of claims 1 to 15, preferably any one of claims 2 to 15, comprising the structure of the compound.

18. Yc is equation (XIII) 【Chemistry 27】 It has the structure of, Preferably, Yc comprises an NH group, preferably a reactive NH group, wherein the NH group enables conjugation of Yc to the portion, and preferably the NH group is structural R ｃ１ Provided by, R ｃ１ CH ２ -R ｃ２ And R ｃ２ The equations are (XXIb), (XIc), and (XIIb) 【Chemistry 28】 A group consisting of any one of the following structures is selected, R ｃ４ is H or methyl, u = 1, 2, 3, 4, or 5. The compound according to any one of claims 1 and 9 to 17.

19. The compound contains a Z group, the Z group is covalently bonded to Yc, preferably to a structure of formula (X), the Z group contains a chelator and optionally a linker, preferably the Z group is R ｃ２ Covalently join to equations (XXIIc), (XId), and (XIId) 【Chemistry 29】 It forms one of the following structures, R ｃ４ is H or methyl, The compound according to any one of claims 1 and 9 to 18, wherein u = 1, 2, 3, 4, or 5.

20. The compound according to any one of claims 1 and 9 to 19, wherein the N-terminal modifying group A is an amino acid Aaa, the compound comprises a Z group covalently bonded to the amino acid Aaa, the Z group comprises a chelator and optionally a linker, and if the linker is present, the linker covalently links the chelator to the amino acid Aaa, preferably to the α-nitrogen of the amino acid Aaa, and preferably the covalent linkage between the linker and the α-nitrogen of the amino acid Aaa is an amide.

21. The compound according to any one of claims 2 to 20, wherein the linker is selected from the group comprising Ttds, O2Oc, Apac, Gly, Bal, Gab, Mamb, Pamba, Ppac, 4Amc, Inp, Sni, Rni, Nmg, Cmp, PEG6, PEG12, and other PEG-amino acids, most preferably Ttds, O2Oc, Apac, 4Amc, PEG6, and PEG12, and preferably the linker amino acid is selected from the group comprising Ttds, O2Oc, and PEG6.

22. An amino acid or peptide is bound to Xaa7, and the amino acid is selected from the group consisting of Asp, asp, Bal, Gly, Gab, Ser, Nmg, Bhf, and Bhk. In the peptide, most of the amino acids of the peptide are charged or polar, and the net charge of the peptide is -2, -1, 0, +1, or +2, preferably the peptide is of formula (XXXa to f) Xaa10-Xaa11-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16 (XXXa) Xaa10-Xaa11-Xaa12-Xaa13-Xaa14-Xaa15 (XXXb) Xaa10-Xaa11-Xaa12-Xaa13-Xaa14 (XXXc) Xaa10-Xaa11-Xaa12-Xaa13 (XXXd) Xaa10-Xaa11-Xaa12 (XXXe) Xaa10-Xaa11 (XXXf) Selected from the group consisting of peptides, Xaa10 is Asp, asp, Bal, Gly, Gab, Ser, Nmg, Bhf, Lys, Ttds, or Bhk, Xaa11 is His, his, Lys, Ttds, Arg, Ape, or Ala, Xaa12 is Phe, Nmf, Tic, Aic, Ppa, Mpa, Amf, Nmf, p he, Lys, Ape, Ttds, and Ppa, Xaa13 is Arg, Lys, Ape, Ttds, or arg, Xaa14 is Asp, Ala, asp, Lys, Ape, or Ttds, Xaa15 is Ttds, Ape, or Lys, Xaa16 is Lys or Ape, as needed, Xaa11 and Xaa12 combine to form a single amino acid selected from the group consisting of Gab, Pamb, Cmp, Pamb, and Mamb, and if necessary, Xaa10, Xaa11, and Xaa12 combine to form a single amino acid selected from the group consisting of Gab, Pamb, Cmp, Pamb, and Mamb. However, in the peptides of formula (XXXa to f), Ape, if present, is the C-terminal construction block. The compound according to any one of claims 1 to 21.

23. The compound according to claim 22, wherein the Z group is covalently bonded to the peptide, and the Z group comprises a chelator and, optionally, a linker.

24. The compound according to any one of claims 2, 5 to 10 and 12 to 22, wherein the Z group is covalently bonded to the amino acid, the Z group comprises a chelator and optionally a linker, and preferably the amino acid is an amino acid bonded to Xaa7, or the amino acid Aaa of the N-terminal modification group A.

25. The compound according to claim 23, wherein the chelator is covalently linked to an amino acid bound to Xaa7, or the chelator is covalently linked to the C-terminal amino acid of the peptide, preferably one of the C-terminal amino acids of the peptides of formula (LI), (LII), (LIIII), and (LIV).

26. The chelators mentioned above are DOTA, DOTAGA, NOTA, NODAGA, NODA-MPAA, HBED, TETA, CB-TE2A, DTPA, DFO, Macropa, HOPO, TRAP, THP, DATA, NOTP, sarcophagin, FSC, NETA, H4octapa, Pycup, N ｘ S ４－ｘ (N4, N2S2, N3S), Hynic, ９９ｍ Tc(CO) ３ - A compound according to any one of claims 2 to 25, more preferably selected from the group consisting of chelators, DOTA, DOTAGA, NOTA, NODAGA, NODA-MPAA, HBED, CB-TE2A, DFO, THP, N4, and most preferably DOTA, DOTAGA, NOTA, NODAGA, and N4.

27. The compound according to claim 26, wherein the chelator is N4Ac.

28. The following formula 【Transformation 30】 compounds H-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-Ttds-Lys(Bio)-NH2 (3BP-2881), The following formula 【Chemistry 31】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-2974), has the following formula 【Chemistry 32】 The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-2975), The following formula 【Transformation 33】 The compound H-met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-2976), The following formula 【Transformation 34】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-Ttds-Lys(DOTA)-NH2 (3BP-3105), The following formula 【Chemistry 35】 The compound DOTA-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-3168), The following formula 【Transformation 36】 The compound DOTA-Ttds-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-3169), The following formula 【Chemistry 37】 The compound DOTA-Ttds-Leu-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-3172), The following formula 【Transformation 38】 The compound Ac-Met-[cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-3175), The following formula 【Chemistry 39】 The compound Ac-met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-3187), The following formula 【Chemistry 40】 The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Nmf-Arg-Asp-NH2 (3BP-3188), The following formula 【Chemistry 41】 The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Tic-Arg-Asp-NH2 (3BP-3189), The following formula 【Chemistry 42】 The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Aic-Arg-Asp-NH2 (3BP-3190), The following formula 【Chemistry 43】 The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Ppa-Arg-Asp-NH2 (3BP-3191), The following formula 【Chemistry 44】 The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Mpa-Arg-Asp-NH2 (3BP-3192), The following formula 【Chemistry 45】 The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Thi-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-3193), The following formula 【Chemistry 46】 The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-Ala-Phe-Arg-Asp-NH2 (3BP-3195), The following formula 【Chemistry 47】 The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Ala-Arg-Asp-NH2 (3BP-3196), The following formula 【Chemistry 48】 The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Ala-NH2 (3BP-319) ８）、 The following formula 【Chemistry 49】 The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-NH2 (3BP-3200), The following formula [Transformation 50] The compound Ac-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-3202), The following formula 【Chemistry 51】 The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Amf-Arg-Asp-NH2 (3BP-3203), The following formula 【Chemistry 52】 The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-his-Phe-Arg-Asp-NH2 (3BP-3210), The following formula 【Chemistry 53】 The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-3211), The following formula 【Chemistry 54】 The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-P he-Cys]-Asp-His-Phe-arg-Asp-NH2 (3BP-3212), The following formula 【Transformation 55】 The compound Ac-Met-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-asp-NH2 (3BP-3213), The following formula 【Transformation 56】 The compound Ac-Met-[Cys(3MeBn)-Gly-Pro-Thr-Glu-Phe-Cys]-Asp-His-Phe-Arg-Asp-NH2 (3BP-3214), The following formula 【Chemistry 57】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Nmf-Arg-Ttds-Lys(DOTA)-NH2 (3BP-3275), The following formula 【Transformation 58】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-phe-Arg-Ttds-Lys(DOTA)-NH2 (3BP-3276), The following formula 【Chemistry 59】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-His-Ppa-arg-Ttds-Lys(DOTA)-NH2 (3BP-3277), The following formula 【Transformation 60】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-NH2 (3BP-3288), The following formula 【Chemistry 61】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-Arg-NH2 (3BP-3299), The following formula 【Transformation 62】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-Gab-Arg-NH2 (3BP-3300), The following formula 【Transformation 63】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-Pamb-Arg-NH2 (3BP-3301), The following formula 【Chemistry 64】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-Cmp-Arg-NH2 (3BP-3302) The following formula 【Transformation 65】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Pamb-Arg-NH2 (3BP-3303), The following formula 【Chemical Formula 66】 The compound DOTA-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-NH2 (3BP-3319), The following formula 【Transformation 67】 The compound DOTA-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-NH2 (3BP-3320), The following formula 【Transformation 68】 The compound DOTA-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-Pamb-Arg-NH2 (3BP-3321), The following formula 【Transformation 69】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-Mamb-Arg-NH2 (3BP-3324), The following formula 【Transformation 70】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-NH2 (3BP-3349), The following formula 【Chemistry 71】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Bal-OH (3BP-3371), The following formula 【Chemistry 72】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-Ttds-Lys(DOTA)-NH2 (3BP-3395), The following formula 【Transformation 73】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-Ttds-Lys(DOTA)-NH2 (3BP-3396), The following formula 【Chemistry 74】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Bhk(DOTA)-OH (3BP-3397), The following formula 【Chemistry 75】 The compound DOTA-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Bal-OH (3BP-3398), The following formula 【Transformation 76】 The compound DOTA-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3401), The following formula 【Chemical Formula 77】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-Ape(DOTA) (3BP-3403), The following formula 【Transformation 78】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-Ttds-Ape(DOTA) (3BP-3404), The following formula 【Chemistry 79】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Otf-Cys]-NH2 (3BP-3409), The following formula 【Chemistry 80】 The compound pentyl NH-urea-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3425), The following formula 【Chemistry 81】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3426), The following formula 【Chemistry 82】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3476), The following formula 【Chemistry 83】 The compound Hex-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Bhk(DOTA-Ttds)-OH (3BP-3489), The following formula 【Chemical 84】 The compound pentyl-SO2-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3514), The following formula 【Chemical 85】 The compound Hex-[Cys(2Lut)-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3518), The following formula 【Chemical 86】 The compound Hex-[Cys(3Lut)-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3519), The following formula 【Chemistry 87】 The compound Hex-[Cys(tMeBn(DOTA-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3555), The following formula 【Chemical 88】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-1Ni-Cys]-OH (3BP-3650), The following formula 【Chemical 89】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Bal-OH (3BP-3651), The following formula 【Chemistry 90】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-NH2 (3BP-3652), The following formula 【Chemistry 91】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Glu-Phe-Cys]-NH2 (3BP-3653), The following formula 【Chemistry 92】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-AET] (3BP-3654), The following formula 【Chemistry 93】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Gly-OH (3BP-3656), The following formula 【Chemical 94】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Gab-OH (3BP-3657), The following formula 【Chemical 95】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Ser-OH (3BP-3658), The following formula 【Chemistry 96】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Nmg-OH (3BP-3659), The following formula 【Chemistry 97】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Bhf-OH (3BP-3660), The following formula 【Chem.98】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Mpa-Cys]-OH (3BP-3664), The following formula 【Chem.99】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-OH (3BP-3665), The following formula 【Chemistry 100】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Nmg-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3678), The following formula 【Chemistry 101】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Hyp-Thr-Gln-Phe-Cys]-OH (3BP-3679), The following formula 【Chemical Engineering 102】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Otf-Cys]-OH (3BP-3680), The following formula 【Chemistry 103】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-asp-NH2 (3BP-3681), The following formula 【Chemical 104】 The compound pentyl-SO2-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3690), The following formula 【Chemistry 105】 The compound pentyl-SO2-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-3691), The following formula 【Chemistry 106】 The compound pentyl-SO2-[Cys(tMeBn(DOTA-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3692), The following formula 【Chemistry 107】 The compound Hex-[Cys(tMeBn(InDOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-NH2 (3BP-3712), The following formula 【Chemistry 108】 The compound Hex-[Cys(tMeBn(InDOTA-AET))-Pro-Pro-Thr-Gln-Phe-AET] (3BP-3713), The following formula 【Chemistry 109】 The compound Hex-[Cys(tMeBn(InDOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Gly-OH (3BP-3714), The following formula 【Chemical 110】 The compound Hex-[Cys(tMeBn(InDOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Nmg-OH (3BP-3715), The following formula 【Chemistry 111】 The compound Hex-[Cys(tMeBn(InDOTA-AET))-Nmg-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3716), The following formula 【Chemistry 112】 The compound pentyl-SO2-[Cys(tMeBn(InDOTA-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3717), is given by the following formula 【Chemistry 113】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Bal-NH2 (3BP-3736), The following formula 【Chemistry 114】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Nmg-NH2 (3BP-3737), The following formula 【Chemical 115】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Nmg-Pro-Thr-Gln-Phe-Cys]-NH2 (3BP-3744), The following formula 【Chemistry 116】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cysol] (3BP-3767), The following formula 【Chemistry 117】 The compound Hex-[Cys(tMeBn(InDOTA-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3770), The following formula 【Chemistry 118】 The compound Hex-[Cys(tMeBn(DOTA-PP))-Nmg-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3771), The following formula 【Chemical 119】 The compound Hex-[Cys-(tMeBn(H-O2Oc-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3967), The following formula 【Chemical 120】 The compound H-Ahx-Ttds-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3980), The following formula 【Chemistry 121】 The compound Hex-[Cys-(tMeBn(H-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-3981), The following formula 【Chemistry 122】 The compound Hex-[Cys-(tMeBn(H-O2Oc-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-4003), The following formula 【Chemical 123】 The compound H-Ahx-Ttds-Nle-[Cys-(tMeBn(DOTA-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-NH2 (3BP-4004), The following formula 【Chemistry 124】 The compound Hex-[Cys-(tMeBn(N4Ac-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4063), The following formula 【Chemistry 125】 The compound Hex-[Cys-(tMeBn(N4Ac-O2Oc-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4088), The following formula 【Chemistry 126】 The compound Hex-[Cys-(tMeBn(H-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4089), The following formula 【Chemistry 127】 The compound Hex-[D-Cys-(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4109), The following formula 【Chemistry 128】 The compound N4Ac-Ttds-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4161), The following formula 【Chemistry 129】 The compound Hex-[Cys-(tMeBn(NODAGA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4162), The following formula 【Chemistry 130】 The compound Hex-[Cys-(tMeBn(N4Ac-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4168), The following formula 【Chemistry 131】 The compound Hex-[Cys-(tMeBn(N4Ac-O2Oc-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4169), The following formula 【Chemistry 132】 The compound Hex-[Cys-(tMeBn(Bio-Ttds-Ttds-Ttds-Ttds-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4170), The following formula 【Chemistry 133】 The compound Hex-[Cys-(tMeBn(H-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4181), The following formula 【Chemistry 134】 The compound Hex-[Cys(tMeBn(ATTO488-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4182), The following formula 【Chemistry 135】 The compound Hex-[Cys-(tMeBn(GaNODAGA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4184), The following formula 【Transformation 136】 The compound Hex-[Cys-(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4186), The following formula 【Chemistry 137】 The compound Hex-[Cys-(tMeBn(DTPA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4214), The following formula 【Chemistry 138】 The compound N4Ac-Ttds-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4219), The following formula 【Chemistry 139】 The compound N4Ac-PEG6-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4221), The following formula [Chemical 140] The compound N4Ac-Glu-Ttds-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4222), The following formula 【Chemistry 141】 The compound Hex-[Cys-(tMeBn(DTPA-O2Oc-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4224), The following formula 【Chemistry 142】 The compound N4Ac-Efa-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4243), The following formula 【Chemistry 143】 The compound N4Ac-gGlu-Ttds-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4245), The following formula 【Chemistry 144】 The compound N4Ac-Glu(AGLU)-Ttds-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4246), has the following formula: 【Chemistry 145】 The compound N4Ac-gGlu-Ttds-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4247), The following formula 【Chemistry 146】 The compound N4Ac-Glu(AGLU)-Ttds-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4249), has the following formula: 【Chemistry 147】 The compound Hex-[Cys-(tMeBn(DOTA-AET))-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4250), The following formula 【Chemistry 148】 The compound Hex-[Cys-(tMeBn(NODAGA-O2Oc-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4251), The following formula 【Chemistry 149】 The compound N4Ac-Glu(AGLU)-Glu(AGLU)-Ttds-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4266), The following formula [Chemical 150] The compound Hex-[Cys-(tMeBn(N4Ac-Ttds-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4299), The following formula 【Chemistry 151】 The compound Hex-[Cys-(tMeBn(N4Ac-PEG6-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4300), The following formula 【Chemistry 152】 The compound Hex-[Cys-(tMeBn(H-SAc-Ser-Ser-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4301), The following formula 【Chemistry 153】 The compound Hex-[Cys-(tMeBn(H-Asp-Asp-Cys-Ttds-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4302), The following formula 【Chemistry 154】 The compound Hex-[Cys-(tMeBn(H-Asp-Asp-Cys-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4303), The following formula 【Chemistry 155】 The compound Hex-[Cys-(tMeBn(H-SAc-Ser-Ser-Ser-Ttds-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3B P-4308) The following formula 【Chemistry 156】 The compound Hex-[Cys-(tMeBn(DTPA2-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4309), The following formula 【Chemistry 157】 The compound Hex-[Cys-(tMeBn(NOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4310), The following formula 【Chemistry 158】 The compound Hex-[Cys-(tMeBn(H-HYNIC-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4342), The following formula 【Chemistry 159】 The compound Hex-[Cys-(tMeBn(NOTA-Ttds-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4344), The following formula [Chemical 160] The compound Hex-[Cys-(tMeBn(DTPA2-Ttds-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4352), The following formula 【Chemistry 161】 The compound Hex-[Cys-(tMeBn(DTPA2-PEG6-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4353), The following formula 【Chemistry 162】 The compound Hex-[Cys-(tMeBn(DTPABzl-Glutar-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4366), has the following formula 【Chemical 163】 The compound Hex-[Cys(tMeBn(LuDOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-Gab-Arg-Ttds-Lys(AF488)-NH2 (3BP-4372), The following formula 【Chemistry 164】 The compound Hex-[Cys(tMeBn(LuDOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-Gab-Arg-Ttds-Ttds-Ttds-Lys(AF488)-NH2 (3BP-4373), The following formula 【Chemistry 165】 The compound Hex-[Cys-(tMeBn(H-HYNIC-Ttds--AET))- Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4376), The following formula 【Chemistry 166】 The compound Hex-[Cys-(tMeBn(PCTA--AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4379), The following formula 【Chemistry 167】 The compound Hex-[Cys-(tMeBn(NOPO--AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4380), The following formula 【Chemical 168】 The compound Hex-[Cys-(tMeBn(HBED--AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4381), The following formula 【Chemistry 169】 The compound Hex-[Cys-(tMeBn(DATA--AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4382), The following formula 【Chemistry 170】 The compound DOTA-Ttds-Nle-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4386), The following formula 【Chemistry 171】 The compound Hex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-Ttds-Lys(DOTA)-NH2 (3BP-4391), The following formula 【Chemistry 172】 The compounds DOTA-Ttds-Nle-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-Ttds-Lys(DOTA)-NH2 (3BP-4392), and The following formula 【Chemistry 173】 The compound DOTA-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Asp-Ttds-Lys(DOTA)-NH2 (3 BP-4393) A compound according to any one of claims 1 to 27, selected from the group consisting of the following.

29. The compound comprises a diagnostically active nuclide or a therapeutically active nuclide, preferably the diagnostically active nuclide is a diagnostically active radionuclide, and more preferably ４３ Sc, ４４ Sc, ５１ Mn, ５２ Mn, ６４ Cd, ６７ Ga, ６８ Ga, ８６ Y, ８９ Zr, ９４ｍ Tc, ９９ｍ Tc, １１１ In, １５２ Tb, １５５ Tb, ２０１ Tl, ２０３ Pb, １８ F, ７６ Br, ７７ Br, １２３ I, １２４ I, １２５ I, preferably ４３ Sc, ４４ Sc, ６４ Cd, ６７ Ga, ６８ Ga, ８６ Y, ８９ Zr, ９９ｍ Tc, １１１ In, １５２ Tb, １５５ Tb, ２０３ Pb, １８ F, ７６ Br, ７７ Br, １２３ I, １２４ I, １２５ I, most preferably ６４ Cd, ６８ Ga, ８９ Zr, ９９ｍ Tc, １１１ In, １８ F, １２３ I, and １２４ A selection from the group consisting of I, wherein the therapeutically active nuclide is a therapeutically active radionuclide, more preferably ４７ Sc, ６７ Cd, ８９ Sr, ９０ Y, １５３ Sm, １４９ Tb, １６１ Tb, １７７ Lu, １８６ Re, １８８ Re, ２１２ Pb, ２１３ Bi, ２２３ Ra, ２２５ Ac, ２２６ Th, ２２７ Th, １３１ I, ２１１ At, preferably ４７ Sc, ６７ Cd, ９０ Y, １７７ Lu, １８８ Re, ２１２ Pb, ２１３ Bi, ２２５ Ac, ２２７ Th, １３１ I, ２１１ At, most preferably ９０ Y, １７７ Lu, ２２５ Ac, ２２７ Th, １３１ I, and ２１１ A compound according to any one of claims 1 to 28, selected from the group consisting of At.

30. For use in a method for diagnosing a disease, for use in a method for treating a disease, for use in a method for identifying a subject in which the subject is likely to respond to treatment for the disease or is likely not to respond, and the method for identifying a subject is a diagnostic method using a compound described in any one of claims 1 to 29, preferably a method for diagnosing a disease as described in any one of claims 1 to 29, or for use in a method for selecting a subject from a group of subjects in which the subject is likely to respond to treatment for the disease or is likely not to respond, and the method for selecting a subject from a group of subjects is A compound according to any one of claims 1 to 29, for use in a diagnostic method using a compound according to any one of claims 1 to 29, preferably a method comprising the step of performing a method for diagnosing a disease as described in any one of claims 1 to 29, or a method for stratifying a group of subjects into subjects likely to respond to treatment for a disease and subjects not likely to respond to treatment for a disease, wherein the method for stratifying the group of subjects is for use in a diagnostic method using a compound according to any one of claims 1 to 29, preferably a method comprising the step of performing a method for diagnosing a disease as described in any one of claims 1 to 29.

31. A composition comprising a compound according to any one of claims 1 to 29 and a pharmaceutically acceptable excipient, preferably a pharmaceutical composition.

32. A kit comprising a compound according to any one of claims 1 to 29, one or more excipients as needed, and one or more devices as needed, wherein the devices are selected from the group including labeling devices, purification devices, handling devices, radiation protection devices, analytical devices, or administration devices.

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