Cyclic polypeptide compound and use thereof

Abstract

The present invention provides a cyclic polypeptide compound and a use thereof. Specifically, provided is a compound represented by formula I or a pharmaceutically acceptable salt thereof. The compound provided by the present invention has good targeting performance and has a wide pharmaceutical prospect.

Description

A cyclic polypeptide compound and its application

[0001] This application claims the benefit of Chinese Patent Application No. 2024100841195, filed January 19, 2024. This application incorporates the entirety of the aforementioned Chinese Patent Application. Technical Field

[0002] The present invention relates to a cyclic polypeptide compound and application thereof. Background Art

[0003] Integrins belong to the cell adhesion receptor family and are transmembrane heterodimers composed of one α subunit and one β subunit. Integrin αvβ3, a key member of the integrin family, is expressed at low or even absent levels in resting endothelial cells and normal tissues, but is highly expressed in some tumor cells and endothelial cells of newly formed blood vessels, garnering considerable attention.

[0004] RGD is a small peptide composed of three amino acids that can specifically bind to a variety of integrin receptors, including integrin αvβ3; 125 I. 99m Tc, 18 F. 68 Ga, 64 Cu, 177 Lu, 225 Ac, etc.) labeling RGD can achieve integrin αvβ3-targeted nuclear medicine imaging (including SPECT, PET / CT) or treatment. Summary of the Invention

[0005] The present invention aims to overcome the limitation of the existing RGD polypeptide compounds, which are limited in variety. To this end, the present invention provides a cyclic polypeptide compound and its application. The compound of the present invention has a novel structure, is easy to prepare, and has broad application prospects.

[0006] The present invention provides a compound represented by formula I or a pharmaceutically acceptable salt thereof;

[0007] in,

[0008] A and B are independently H or a fragment of formula I-1:

[0009] R 1 Independently C6-C 14 Aryl or 1, 2 or 3 R 1-1 Substituted C6-C 14 Aryl; R 1-1 is C1-C6 alkyl, hydroxy or halogen;

[0010] R 2 are independently carboxyl (-COOH) or amide (-CONH2);

[0011] R 3 independently -C1-C6 alkylene-urea (-NH(C=NH)NH2);

[0012] A and B are not H at the same time;

[0013] -L1- and -L3- are independently a single bond, -C1-C6 alkylene-NHCO-, -C1-C6 alkylene-NHCO-C1-C6 alkylene-, -C1-C6 alkylene-C1-C6 alkylenethio-NHCO-, -C1-C6 alkylene-C1-C6 alkyleneoxy-NHCO-, -C1-C6 alkylene-CONHCO-, -C1-C6 alkylene-NHCO-C1-C6 alkylene-SCO-C1-C6 alkylene-NHCO-;

[0014] -L2- is -NHCO-, -NHCO-C1-C6 alkylene-NHCO- or a single bond;

[0015] L is The "*" end is connected to L2;

[0016] T and W are independently C1-C6 alkylene;

[0017] X is

[0018] Y is a single bond, The "*" end is connected to W;

[0019] n1 is an integer from 1 to 20;

[0020] n2 is an integer from 1 to 10;

[0021] G consists of a chelating group and a diagnostic radionuclide; or, a chelating group and a therapeutic radionuclide.

[0022] In one embodiment, in the compound represented by Formula I and its pharmaceutically acceptable salt, the definitions of certain groups may be as described below, and the definitions of other groups may be as described in any embodiment of the present invention (hereinafter referred to as "one embodiment"):

[0023] In one scheme, R 1 In the C6-C 14 Each aryl group is independently phenyl or naphthyl, for example phenyl.

[0024] In one scheme, R 1-1 wherein the halogen is fluorine, chlorine or bromine.

[0025] In one scheme, R 1-1 wherein the C1-C6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl or n-pentyl.

[0026] In one scheme, -L3-, -L2-, -L1-, R 3 , T and W, the C1-C6 alkylene group is each independently a methylene group, an ethylene group, a n-propylene group, an isopropylene group, a n-butylene group, an isobutylene group, a tert-butylene group or a n-pentylene group.

[0027] In one embodiment, in -L3- and -L1-, the C1-C6 alkylenethio groups are each independently methylenethio, ethylenethio, n-propylenethio, isopropylidenethio, n-butylidenethio, isobutylidenethio, tert-butylidenethio or n-pentylidenethio.

[0028] In one embodiment, in -L3- and -L1-, the C1-C6 alkyleneoxy group is independently a methyleneoxy group, an ethyleneoxy group, a n-propyloxy group, an isopropyloxy group, a n-butyloxy group, an isobutyloxy group, a tert-butyloxy group or a n-pentyloxy group.

[0029] In one embodiment, n1 is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16, for example, n1 is an integer from 1 to 10, and for example, n1 is 2.

[0030] In one embodiment, n2 is 1, 2, 3, 4, 5, 6, 7, 8 or 9, for example, n2 is an integer from 1 to 5, and for example, n2 is 1.

[0031] In one embodiment, in G, the chelating group is a conventional chelating group in the art, such as 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA), 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), 2-(4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane-1-yl) glutaric acid (DOTA-GA), 2-(4,7-bis(carboxymethyl)-1,4,7-triazononan-1-yl) glutaric acid (NODA-GA), diethylenetriaminepentaacetic acid (DTPA), N,N'-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid (HBED-CC) or a chelating group obtained by removing one hydroxyl group (-OH) from thioacetyl triglycine (MAG3), for example

[0032] In one embodiment, in G, the diagnostic radionuclide is conventional in the art, for example 18 F. 68 Ga, 99m Tc or64 Cu.

[0033] In one embodiment, in G, the therapeutic radionuclide is conventional in the art, for example 212 Pb, 211 At 177 Lu, 188 Re、 225 Ac or 67 Cu.

[0034] In a certain embodiment of the present invention, the valence state of the diagnostic radionuclide is monovalent, divalent, trivalent or tetravalent, for example, trivalent.

[0035] In one embodiment of the present invention, the valence state of the therapeutic radionuclide is monovalent, divalent, trivalent or tetravalent, for example, trivalent.

[0036] In one embodiment, -L1- and -L3- are independently a single bond, *-C1-C6 alkylene-NHCO-, *-C1-C6 alkylene-NHCO-C1-C6 alkylene-, *-C1-C6 alkylene-C1-C6 alkylenethio-NHCO-, *-C1-C6 alkylene-C1-C6 alkyleneoxy-NHCO-, *-C1-C6 alkylene-CONHCO-, *-C1-C6 alkylene-NHCO-C1-C6 alkylene-SCO-C1-C6 alkylene-NHCO-, wherein the "*" end is connected to A or B.

[0037] In one embodiment, -L2- is -NHCO-*, -NHCO-C1-C6 alkyl-NHCO-* or a single bond, wherein the "*" end is connected to L.

[0038] In one scheme, R 1 Independently C6-C 14 Aryl.

[0039] In one embodiment, -L1-, -L3- and -L2- are not single bonds at the same time.

[0040] In one embodiment, -L1- and -L3- are independently -C1-C6 alkylene-NHCO-C1-C6 alkylene-.

[0041] In one embodiment, -L2- is -NHCO-C1-C6 alkylene-NHCO-;

[0042] In one solution, Y is

[0043] In one solution, n1 is 2.

[0044] In one scheme, G is composed of and 177Lu chelate composition, e.g.

[0045] In one plan, for

[0046] In one scheme, -L- is X, n1 and n2 are independently as described in any one of the present invention, wherein the "*" end is connected to L2. Preferably, -L- is The "*" end is connected to L2.

[0047] In one scheme, -L- is

[0048] The "*" end is connected to L2.

[0049] In one embodiment, the compound represented by formula I is

[0050] The present invention provides a compound represented by formula II or a pharmaceutically acceptable salt thereof;

[0051] Among them, G1 is composed of a chelating group and a non-radioactive nuclide;

[0052] The chelating group, A, B, -L1-, -L3-, -L2- and -L- are independently as described in any embodiment of the present invention.

[0053] The present invention provides a compound represented by formula I-2 or a pharmaceutically acceptable salt thereof;

[0054] Wherein, g is a chelating group;

[0055] The chelating group, A, -L1-, -L2-, -L3-, -L- and B are independently as described in any embodiment of the present invention.

[0056] In one embodiment, the compound represented by formula I-2 is

[0057] The present invention provides a compound represented by formula I-3;

[0058] Wherein, E is an alkynyl group or azido (-N3);

[0059] Said T, A, -L1-, -L2-, -L3- and B are independently as described in any embodiment of the present invention.

[0060] In one embodiment, the compound represented by formula I-3 is

[0061] The present invention provides a pharmaceutical composition comprising a compound of Formula I, a compound of Formula II, a compound of Formula I-2, or a pharmaceutically acceptable salt thereof (referring to a compound of Formula I, a compound of Formula II, or a compound of Formula I-2) and a pharmaceutical excipient.

[0062] The present invention also provides a kit comprising a compound of Formula I, a compound of Formula II, a compound of Formula I-2, or a pharmaceutically acceptable salt thereof (referring to a compound of Formula I, a compound of Formula II, or a compound of Formula I-2) and instructions.

[0063] The present invention also provides a use of the compound of Formula I, the compound of Formula I-2, or a pharmaceutically acceptable salt thereof (referring to the compound of Formula I or the compound of Formula I-2) as described above in the preparation of a developer for diagnosing tumors.

[0064] The present invention also provides a use of the compound represented by Formula I, the compound represented by Formula I-2, or a pharmaceutically acceptable salt thereof (referring to the compound represented by Formula I or the compound represented by Formula I-2) as described above in the preparation of a drug for treating and / or preventing tumors.

[0065] In certain preferred embodiments of the present invention, the tumor is a solid tumor, such as lung cancer, colorectal cancer or pancreatic cancer.

[0066] Explanation of terms:

[0067] The term "pharmaceutically acceptable salt" refers to a salt formed by reacting a compound with a pharmaceutically acceptable (relatively non-toxic, safe, and suitable for patient use) acid or base. When the compound contains a relatively acidic functional group, a base addition salt can be obtained by contacting the free form of the compound with a sufficient amount of a pharmaceutically acceptable base in a suitable inert solvent. When the compound contains a relatively basic functional group, an acid addition salt can be obtained by contacting the free form of the compound with a sufficient amount of a pharmaceutically acceptable acid in a suitable inert solvent.

[0068] The term "halogen" refers to fluorine, chlorine, bromine or iodine.

[0069] The term "alkyl" refers to a straight or branched chain alkyl group having a specified number of carbon atoms (e.g., C1 to C6). Alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, n-pentyl, n-hexyl, and the like.

[0070] In the present invention, the term "alkylene" refers to a saturated linear or branched divalent hydrocarbon group.1-6 Alkylene refers to an alkylene group having 1 to 6 carbon atoms, and specific examples thereof include methylene, ethylene (e.g., -CH2CH2-, -CH(CH3)-), propylene (e.g., -CH2CH2CH2-, -C(CH3)2-, -CH2CH(CH3)-), butylene (e.g., -CH2CH2CH2CH2-, -CH(CH3)CH(CH3)-, -CH2CH(CH3)CH2-), n-pentylene or n-hexylene.

[0071] In the present invention, the term "alkyleneoxy" refers to -O-alkylene-, wherein alkylene is as defined above.

[0072] In the present invention, the term "alkylenethio" refers to -S-alkylene-, wherein alkylene is as defined above.

[0073] The term "aryl" refers to a group having a specified number of carbon atoms (e.g., C6 to C 10 ) is a cyclic group consisting only of carbon atoms, which is a monocyclic or condensed ring. Aryl includes but is not limited to phenyl or naphthyl.

[0074] The terms "pharmaceutically acceptable excipients" and "pharmaceutical excipients" refer to excipients and additives used in the production of pharmaceuticals and in the preparation of prescriptions. They are all substances contained in pharmaceutical preparations, other than the active ingredient. For details, see the Pharmacopoeia of the People's Republic of China (2020 edition) or the Handbook of Pharmaceutical Excipients (Raymond C Rowe, 2009).

[0075] The term "treat" refers to any of the following: (1) alleviating one or more biological manifestations of a disease; (2) interfering with one or more points in the biological cascade that leads to a disease; or (3) slowing the progression of one or more biological manifestations of a disease.

[0076] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain preferred embodiments of the present invention.

[0077] The reagents and raw materials used in the present invention are commercially available.

[0078] The positive progress of the present invention is that the compound of the present invention has a novel structure and a high level of specific tumor uptake. BRIEF DESCRIPTION OF THE DRAWINGS

[0079] Figure 1 177 SPECT / CT imaging of Lu-DOTA-Tri-RGD in mice after 0.5 h;

[0080] Figure 2 177SPECT / CT imaging of Lu-DOTA-Tri-RGD in mice after 1 hour;

[0081] Figure 3 177 SPECT / CT imaging of Lu-DOTA-Tri-RGD in mice after 4 hours;

[0082] Figure 4 shows 177 SPECT / CT imaging of Lu-DOTA-Tri-RGD in mice after 10 hours;

[0083] Figure 5 177 SPECT / CT imaging of Lu-DOTA-Tri-RGD in mice for 24 hours;

[0084] Figure 6 177 SPECT / CT imaging of Lu-DOTA-Tri-RGD in mice after 48 hours;

[0085] Figure 7 177 SPECT / CT imaging of Lu-DOTA-RGD in mice after 0.5 h;

[0086] Figure 8 177 SPECT / CT imaging of Lu-DOTA-RGD in mice after 1 hour;

[0087] Figure 9 177 SPECT / CT imaging of Lu-DOTA-RGD in mice after 4 hours;

[0088] Figure 10 177 SPECT / CT imaging of Lu-DOTA-RGD in mice after 10 hours;

[0089] Figure 11 177 SPECT / CT imaging of Lu-DOTA-RGD in mice for 24 hours;

[0090] Figure 12 177 SPECT / CT images of Lu-DOTA-RGD in mice after 48 hours. DETAILED DESCRIPTION

[0091] The present invention is further illustrated by way of examples below, but the present invention is not limited to the scope of the examples. Experimental methods in the following examples where specific conditions are not specified were performed according to conventional methods and conditions, or selected according to the product specifications.

[0092] Example 1 177 Preparation of Lu-DOTA-Tri-RGD

[0093] 1. Radionuclides 177 Lu-labeled DOTA-N3

[0094] 177 The hydrochloric acid solution of Lu is 177 A mixed solution of LuCl3 and 0.04 mol / L hydrochloric acid, wherein 177 The radioactivity of Lu is 11.4 mCi. The acetic acid / sodium acetate solution of DOTA-N3 (Formula 12) is a mixed solution prepared by dissolving DOTA-N3 (Formula 12) in a 0.5 M acetic acid-sodium acetate solution with a pH of 5.2±0.1, wherein the DOTA-N3 concentration is 0.30 mg / mL.

[0095] Add 12 μL 177 Lu hydrochloric acid solution (11.4 mCi) and 90 μL of LOTA-N3 (Formula 12) in acetic acid / sodium acetate solution (0.30 mg / mL) were mixed and heated at 95°C for 15 min to obtain 177 The labeling rate of Lu-DOTA-N3 by Radio-HPLC was 86.02%, as shown in Table 1. The labeled product was purified by C18 column to obtain a product with a radiochemical purity of 94.18%, as shown in Table 2.

[0096] Table 1

[0097] Table 2

[0098] Radio-HPLC detection conditions:

[0099] Chromatographic column: ZORBAX Eclipse Plus C18 (4.6 mm × 250 mm, 5 μm)

[0100] Mobile phase: A: 0.1% TFA in H2O, B: 0.1% TFA in CH3CN

[0101] Gradient: 0-5-10-14-15-17 min, 1-1-10-10-1-1% B

[0102] Flow rate: 1 mL / min

[0103] Wavelength: 220nm

[0104] Column temperature: 30°C

[0105] C18 column purification conditions:

[0106] Activation of C18 cartridge (Waters, Sep-Pak Light-C18 solid phase extraction cartridge): first elute with 5 mL of ethanol

[0107] The C18 column was then rinsed with 5 mL of deionized water.

[0108] Purify the product with a C18 column: dilute the reaction solution with 1 mL of sterile water for injection and pass it through the C18 column; rinse the C18 column with 0.5 mL of sterile water for injection to remove radioactive impurities; and rinse the C18 column with anhydrous ethanol to obtain the target product. 177 Lu-DOTA-N3.

[0109] 2. Preparation of Formula 13 (RGD-alkynyl)

[0110] N-(tert-Butyloxycarbonyl)-L-glutamic acid (Boc-Glu-OH, 1 eq) was dissolved in DMF, 1,3-dicyclohexylcarbodiimide (DCC, 1 eq) and N-hydroxysuccinimide (HOSu, 3 eq) were added, and the reaction was carried out for 5 minutes. Compd 1 (1 eq) was then added and the reaction was carried out at room temperature for 2 hours. The reaction was monitored by LC-MS. After the raw material was completely reacted, TFA was added, the mixture was concentrated in vacuo, and the mixture was washed with ether twice to obtain the crude product Compd 2.

[0111] Boc-β-Ala-OH (1 eq) was dissolved in DMF, and 2-succinimidyl-1,1,3,3-tetramethyluronium tetrafluoroborate (TSTU, 1 eq) was added to react for 5 min. Compd 2 (1 eq) was then added to react at room temperature for 2 h. The reaction was monitored by LC-MS. After the raw material was completely reacted, TFA was added, the mixture was concentrated in vacuo, and the mixture was washed with ether twice to obtain Compd 3 as a crude product.

[0112] Compd3 (1 eq) was dissolved in DMF, and then N,N-diisopropylethylamine (DIPEA, 5 eq) and Compd4 (2 eq) were added in sequence. The mixture was fully reacted at room temperature for 2 hours and monitored by LC-MS. After the raw material reacted completely, the mixture was concentrated in vacuo, dried, and purified by reverse phase to obtain the target product Formula 13 (RGD-alkynyl) (25 mg, 35%).

[0113] 3. 77 Preparation of Lu-DOTA-Tri-RGD

[0114] Preparation of RGD-alkynyl solution: The obtained RGD-alkynyl (Formula 13) was dissolved in DMF, wherein the concentration of RGD-alkynyl was 0.7 mg / mL.

[0115] Preparation of copper sulfate solution: Dissolve copper sulfate in 0.5 M acetic acid-sodium acetate buffer solution with a pH of 5.2±0.1, wherein the concentration of copper sulfate is 3.2 mg / mL.

[0116] Preparation of sodium ascorbate solution: Sodium ascorbate was dissolved in 0.5 M acetic acid-sodium acetate buffer solution with a pH of 5.2±0.1, wherein the concentration of sodium ascorbate was 16 mg / mL.

[0117] 45 μL of RGD-alkynyl (0.7 mg / mL) (Formula 13) solution was mixed with the purified 177 The Lu-DOTA-N3 reaction solution (30 μL), 20 μL of 0.5 M acetic acid-sodium acetate buffer (pH = 5.2 ± 0.1), 15 μL of copper sulfate solution (3.2 mg / mL), and 17 μL of sodium ascorbate solution (16 mg / mL) were mixed and heated at 40°C for 60 min to obtain 177 The reaction solution of Lu-DOTA-Tri-RGD was 127 μL, and the radiochemical purity was 95.57% as determined by Radio-HPLC (see Table 3).

[0118] Table 3

[0119] Radio-HPLC detection conditions:

[0120] Chromatographic column: ZORBAX Eclipse Plus C18 (4.6 mm × 250 mm, 5 μm)

[0121] Mobile phase: A: 0.1% TFA in H2O, B: 0.1% TFA in CH3CN

[0122] Gradient: 0-10-20-30-35-38-40-45 min, 1-10-20-40-40-100-1-1% B

[0123] Flow rate: 1 mL / min

[0124] Wavelength: 220nm

[0125] Column temperature: 30°C

[0126] Effect Test Example 1

[0127] 1. In vitro stability

[0128] The reaction solution after the reaction in Example 1 ( 177Lu-DOTA-Tri-RGD, 20 μL) was diluted with 1 mL of 0.5 M acetic acid-sodium acetate buffer (pH = 5.2) and placed in a 25° C. stability test chamber. After 24 hours, the radiochemical purity of the product remained essentially unchanged at 95.38%.

[0129] 2. Biodistribution

[0130] Control compound: 177 Lu-DOTA-RGD, the structure is shown below,

[0131] Preparation method refers to existing literature Shi, J., Liu, Z., Jia, B., Yu, Z., Zhao, H., & Wang, F. Potential therapeutic radiotracers: preparation, biodistribution and metabolic characteristics of 177 Lu-labeled cyclic RGDfK dimer.Amino Acids,2009,39(1),111–120 (ie the compound in the literature 177 Lu-DOTA-RGD2).

[0132] U87MG male tumor-bearing nude mice (Shanghai Junna Medical Technology Co., Ltd., No. 202347670) were used to inject radiolabeled compounds into the 177 Lu-DOTA-Tri-RGD (1 mCi / mL, obtained by diluting the reaction solution obtained in Example 1 with acetic acid-sodium acetate buffer solvent (0.5 mol / L, pH 5.2±0.1)) was injected into mice via the tail vein (approximately 100 μCi / mouse). The animals were sacrificed 0.5 h, 1 h, 4 h, and 24 h after injection, and the tissues and organs of interest were dissected and weighed. The radioactivity counts were measured using a gamma counter, and the ID% / g of the tissues and organs were calculated (ID% / g = tissue count / total count in the injected mouse / tissue weight*100%).

[0133] In this embodiment, 177 The organ distribution of Lu is shown in Table 4 and Table 5. 177 Compared with Lu-DOTA-RGD, 177 Lu-DOTA-Tri-RGD showed high specific tumor uptake; after 24 hours, renal absorption was close to complete metabolism (1.09±0.11ID% / g), and tumor uptake remained at a level comparable to that reported in the literature; after 24 hours, it still had a high tumor-to-background ratio (tumor / blood: 100; tumor / muscle: 11.11).

[0134] Table 4 177 Lu-DOTA-Tri-RGD and 177 Comparison of Lu-DOTA-RGD uptake in various tissues of U87MG tumor-bearing mice 24 hours after administration (unit: ID% / g)

[0135] Table 5 177 Comparison of Lu-DOTA-Tri-RGD uptake in various tissues of U87MG tumor-bearing mice at different time points after administration (unit: ID% / g)

[0136] Effect Test Example 2: Small Animal SPECT / CT Imaging

[0137] Using U87MG glioblastoma model mice, radiolabeled compounds were injected into 177 Lu-DOTA-Tri-RGD injection (1 mCi / mL, obtained by diluting the reaction solution obtained in Example 1 with acetic acid-sodium acetate buffer solvent (0.5 mol / L, pH 5.2±0.1)) and containing 177 Lu-DOTA-RGD solution was injected into mice via the tail vein (about 600 μCi / mouse, 5 mice each), and in vivo scanning was performed on the animals at 0.5 h, 1 h, 4 h, 10 h, 24 h, and 48 h after injection. The results are shown in Figures 1 to 12.

[0138] For the two compounds, the model mice still had good tumor uptake at 24h, but we designed 177 The uptake of Lu-DOTA-Tri-RGD in normal tissues was significantly lower than 177 Lu-DOTA-RGD, and its clearance rate in normal tissues is higher than 177 Lu-DOTA-RGD.

Claims

1. A compound of formula I or a pharmaceutically acceptable salt thereof; Wherein, A and B are independently H or a fragment represented by Formula I-1: R 1 Independently C6-C 14 aryl or C6-C 1-1 aryl substituted with one, two or three R 14 ; R 1-1 is C1-C6 alkyl, hydroxy or halogen; R 2 Independently -COOH or -CONH2; R 3 independently -C1-C6 alkylene -NH(C=NH)NH2; A and B are not both H at the same time; -L1- and -L3- are independently a single bond, -C1-C6 alkylene-NHCO-, -C1-C6 alkylene-NHCO-C1-C6 alkylene-, -C1-C6 alkylene-C1-C6 alkylthio-NHCO-, -C1-C6 alkylene-C1-C6 alkoxy-NHCO-, -C1-C6 alkylene-CONHCO-, -C1-C6 alkylene-NHCO-C1-C6 alkylene-SCO-C1-C6 alkylene-NHCO-; -L2- is -NHCO-, -NHCO-C1-C6 alkylene-NHCO- or a single bond; L is wherein the "*" end is connected to L2; T and W are independently C1-C6 alkylene; X is Y is a single bond, wherein the "*" end is connected to W; n1 is an integer from 1 to 20; n2 is an integer from 1 to 10; G is composed of a chelating group and a diagnostic radionuclide; or, a chelating group and a therapeutic radionuclide.

2. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that, The compound represented by Formula I satisfies one or more of the following conditions: (1)R 1 Among them, the C6-C 14 aryl groups are each independently phenyl or naphthyl, such as phenyl; (2)R 1-1 wherein the halogen is fluorine, chlorine or bromine; (3)R 1-1 wherein each of the C1-C6 alkyl groups is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl or n-pentyl; (4)-L3-, -L2-, R 3 , -L1-, T and W, each of said C1-C6 alkylene groups is independently methylene, ethylene, n-propylene, isopropylidene, n-butylene, isobutylene, tert-butylene or n-pentylene; (5) In -L3- and -L1-, the C1-C6 alkylthio is independently methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, tert-butylthio or n-pentylthio; (6) In -L3- and -L1-, the C1-C6 alkoxy is independently methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy or n-pentyloxy; (7) n1 is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or 16, for example, n1 is an integer from 1 to 10, or n1 is 2; (8) n2 is 1, 2, 3, 4, 5, 6, 7, 8 or 9, for example, n2 is an integer from 1 to 5, or n2 is 1; In (9)G, the chelating group is a chelating group obtained by removing one hydroxyl group from 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid, 1,4,7-triazacyclononane-1,4,7-triacetic acid, 2-(4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl)glutaric acid, 2-(4,7-bis(carboxymethyl)-1,4,7-triazanon-1-yl)glutaric acid, diethylenetriaminepentaacetic acid, N,N′-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid or mercaptoacetyltriglycine, for example In (10)G, the diagnostic radionuclide is 18 F, 68 Ga, 99m Tc or 64 Cu; (11) The valence state of the diagnostic radionuclide is monovalent, divalent, trivalent or tetravalent, for example, trivalent; In (12)G, the therapeutic radionuclide is 212 Pb, 211 At, 177 Lu, 188 Re, 225 Ac or 67 Cu; (13) The valence state of the therapeutic radionuclide is monovalent, divalent, trivalent or tetravalent, for example, trivalent.

3. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that, The compound represented by Formula I satisfies one or more of the following conditions: (1) -L1- and -L3- are independently a single bond, *-C1-C6 alkylene-NHCO-, *-C1-C6 alkylene-NHCO-C1-C6 alkylene-, *-C1-C6 alkylene-C1-C6 alkylthio-NHCO-, *-C1-C6 alkylene-C1-C6 alkoxy-NHCO-, *-C1-C6 alkylene-CONHCO-, *-C1-C6 alkylene-NHCO-C1-C6 alkylene-SCO-C1-C6 alkylene-NHCO-, wherein the "*" end is connected to A or B; (2) -L2- is -NHCO-*, -NHCO-C1-C6 alkyl-NHCO-* or a single bond, wherein the "*" end is connected to L.

4. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1, wherein, The compound represented by Formula I satisfies one or more of the following conditions: (1)R 1 independently C6-C 14 aryl; (2) -L1-, -L3- and -L2- are not all single bonds at the same time; (3) -L1- and -L3- are independently C1-C6 alkylene-NHCO-C1-C6 alkylene-; (4) -L2- is -NHCO-C1-C6 alkylene-NHCO-; (5)Y is (6) n1 is 2; Preferably, -L- is wherein the "*" end is connected to L2, and X, n1 and n2 are independently as described in claim 1; Further preferably, -L- is n1 and n2 are independently as described in claim 1; wherein the "*" end is connected to L2; For example, -L- is wherein the "*" end is connected to L2; (7) G consists of and 177 a Lu chelate composition, for example 5. The compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1, characterized in that, For 6. The compound of formula I or a pharmaceutically acceptable salt thereof as claimed in claim 1, characterized in that, The compound represented by Formula I is 7. A compound of formula II or a pharmaceutically acceptable salt thereof; Among them, G1 consists of a chelating group and a non-radioactive nuclide; The chelating group, A, B, -L1-, -L3-, -L2- and -L- are independently as described in any one of claims 1-6.

8. A compound of formula I-2 or a pharmaceutically acceptable salt thereof; Among them, g is a chelating group; The chelating group, A, -L1-, -L2-, -L3-, -L- and B are independently as described in any one of claims 1-6; Preferably, the compound represented by Formula I-2 is 9. A compound represented by Formula I-3; Among them, E is an alkynyl or azide group; The T, A, -L1-, -L2-, -L3- and B are independently as described in any one of claims 1-6; Preferably, the compound represented by Formula I-3 is 10. A pharmaceutical composition comprising a compound of formula I as described in any one of claims 1-6 or a pharmaceutically acceptable salt thereof, a compound of formula II as described in claim 7 or a pharmaceutically acceptable salt thereof, a compound of formula I-2 as described in claim 8 or a pharmaceutically acceptable salt thereof, and a pharmaceutical excipient.

11. A kit comprising a compound of formula I as described in any one of claims 1-6 or a pharmaceutically acceptable salt thereof, a compound of formula II as described in claim 7 or a pharmaceutically acceptable salt thereof, a compound of formula I-2 as described in claim 8 or a pharmaceutically acceptable salt thereof, and an instruction manual.

12. Use of a compound of formula I as described in any one of claims 1-6 or a pharmaceutically acceptable salt thereof, a compound of formula I-2 as described in claim 8 or a pharmaceutically acceptable salt thereof in the preparation of a contrast agent for tumor diagnosis; For example, the tumor is a solid tumor, preferably lung cancer, rectal cancer or pancreatic cancer.

13. Use of a compound of formula I as described in any one of claims 1-6 or a pharmaceutically acceptable salt thereof, a compound of formula I-2 as described in claim 8 or a pharmaceutically acceptable salt thereof in the preparation of a drug for the treatment and / or prevention of tumors; For example, the tumor is a solid tumor, such as lung cancer, rectal cancer or pancreatic cancer.

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