WO2025108141A1 - Radiolabeled elastin-like polypeptide, preparation method therefor and use thereof - Google Patents

Abstract

Provided are a radiolabeled elastin-like polypeptide, a preparation method therefor and the use thereof. The elastin-like polypeptide is linked with a radionuclide. By means of direct or interventional intratumor injection and by means of using thermosensitive agglutination and crosslinking characteristics of the ELP, the present invention can retain the radionuclide in tumors. Accordingly, the present invention can accurately control the radiation dose, set a target area and a safety boundary and kill tumor cells in a close range, thus making advanced tumors reduced or disappear, and achieving the purposes of improving the survival quality and prolonging the survival period.

Description

A radioactively labeled elastin-like polypeptide and its preparation method and application Technical Field

The present invention relates to the field of biomedicine, and in particular to a radioactively labeled elastin-like polypeptide and a preparation method and application thereof.

Background Art

Cancer is a series of diseases caused by multiple gene mutations caused by environmental influences, somatic DNA replication errors and inherited defects. The phenotype of cancer is the uncontrolled growth of abnormal cells, unlimited replication and invasion of surrounding normal tissues. 85% of cancer patients have solid tumors, and 50% of them die from malignant diseases. Tumor metastasis is often the final cause of death, but the failure of treatment will lead to aggravation of metastasis due to the loss of control of the primary tumor. In the cervix, colon, ovary and pancreas, the control of primary tumors is particularly difficult. Therefore, there is an urgent need to improve the treatment of primary tumors. Tumor treatment mainly includes traditional surgical treatment, radiotherapy and chemotherapy. In general, radiotherapy and chemotherapy are mainly targeted at rapidly proliferating cells, but cancer cells are not the only rapidly proliferating cells in the body, and their toxic side effects are common in hematopoietic progenitor cells in the bone marrow and intestinal epithelial cells. Surgery involves the removal of the tumor itself, which has limited effects on normal tissues, it is difficult to define the tumor margins, and metastases are too small to be successfully removed by surgery.

The purpose of drug delivery in cancer treatment is to increase the concentration of drugs in tumors and limit systemic exposure. Many delivery drugs have been developed to achieve this goal, such as liposomes, micelles, affinity-targeted drugs, and macromolecular carriers. How to overcome the limitations of tumor-targeted therapy? The discovery of elastin-like peptides as drug storage materials provides a therapeutic means for tumor treatment.

Elastin-like polypeptides (ELPs) are temperature-sensitive biopolymers composed of Val-Pro-Gly-Xaa-Gly, a pentapeptide repeating sequence, derived from the hydrophobic structural region of mammalian elastin. Elastin-like polypeptides undergo a sharp reversible phase transition due to temperature increase, also known as the low critical solution temperature. Elastin-like polypeptides are soluble in aqueous solution at the hell transition temperature, but above the critical temperature, the cross-linking and aggregation between the molecular chains of elastin-like polypeptides become insoluble and aggregate and precipitate, making the elastin-like polypeptides become ordered polymers in an aqueous environment. This phase transition is reversible, and the phase transition temperature can also be adjusted by adjusting the type, molecular weight and concentration of Xaa. Therefore, the characteristics and treatment needs of different drugs, the release and targeting of drugs in time and space, can be precisely controlled by adjusting the phase transition temperature of elastin-like polypeptide sequences and lengths.

Moreover, elastin-like proteins can be expressed by connecting the sequence of the active protein with the elastin-like polypeptide through genetic engineering, or by designing certain active groups, and then chemically reacting with the drug to covalently conjugate the drug to the elastin-like polypeptide chain to form ELPs-drug conjugates. Elastin-like polypeptides act as drug carriers to treat a variety of diseases, such as siEVI1-ELP for various cancers (breast cancer, ovarian cancer, pancreatic cancer and lung cancer), VIP-ELP for the treatment of pulmonary hypertension, cardiomyopathy and cystic fibrosis, and GLP1-ELP for the treatment of type 2 diabetes.

In addition, because elastin-like polypeptides have excellent pharmacokinetic characteristics, physiological half-life, and can be decomposed into biosafe by-products, they can be injected into the tumor site to form micellar gels, which can achieve slow release of drugs in the body and form reservoirs in the body, thereby achieving long-term effectiveness of the drugs and local delivery of the drugs.

The radioactive isotope-labeled elastin-like polypeptide designed by the present invention can be accurately injected into the tumor body. Due to the phase change characteristics of elastin-like, once it enters the tumor body, it can be fixed in the tumor. The radiation effect of the radioactive isotope kills the cancer cells, thereby causing the death of cancer cells, accurately eliminating or reducing tumor tissue, and has broad application prospects in biomedical research, drug development and clinical diagnosis.

Summary of the invention

To address the deficiencies of the prior art, the present invention aims to provide an elastin-like polypeptide and a method for combining the polypeptide with a radionuclide, as well as the use of the elastin-like polypeptide as a drug carrier.

To achieve the above object, the present invention adopts the following technical solutions.

On the one hand, the present invention provides a radionuclide-labeled elastin-like polypeptide, wherein the radionuclide-labeled elastin-like polypeptide structure is composed of an elastin-like polypeptide _P1 represented by (VPGXG)n and a) a metal chelator complexed with a metal radionuclide; or is composed of an elastin-like polypeptide _P1 represented by (VPGXG)n and b) a tail peptide _P2 bound to a radioactive halogen; wherein,

X includes I, A and F, and n is selected from 20 to 120;

The metal chelator is selected from DOTA, DTPA, and NOTA;

The amino acid sequence of the tail peptide _P2 that binds to the radioactive halogen is selected from the group consisting of YGYGYGYGYGYGY;

The radioactive halogen is selected from ¹⁸ F, ¹²³ I, ¹²⁴ I, ¹²⁵ I, ¹³¹ I, ²¹¹ At;

The metal radionuclide is selected from ⁶⁴ Cu, ⁶⁷ Cu, ⁶⁸ Ga, ⁸⁹ Zr, ¹⁷⁷ Lu, ⁴⁴ Sc, ¹¹¹ In, ⁹⁰ Y, ^99m Tc, ¹⁵³ Sm, ¹⁵³ Gd, ¹⁵⁵ Gd, ¹⁵⁷ Gd, ²¹³ Bi, ²²³ Ra, ²²⁵ Ac.

In some embodiments, the radionuclide-labeled elastin-like polypeptide structure consists of an elastin-like polypeptide _P1 represented by (VPGXG)n and a) a metal chelator complexed with a metal radionuclide; wherein,

X includes I, A and F, and n is selected from 20 to 120;

The metal chelator is selected from DOTA, DTPA, and NOTA;

The metal radionuclide is selected from ⁶⁴ Cu, ⁶⁷ Cu, ⁶⁸ Ga, ⁸⁹ Zr, ¹⁷⁷ Lu, ⁴⁴ Sc, ¹¹¹ In, ⁹⁰ Y, ^99m Tc, ¹⁵³ Sm, ¹⁵³ Gd, ¹⁵⁵ Gd, ¹⁵⁷ Gd, ²¹³ Bi, ²²³ Ra, ²²⁵ Ac.

In some embodiments, the radionuclide-labeled elastin-like polypeptide structure is represented by (VPGXG)n The invention is composed of an elastin-like polypeptide P ₁ and a tail peptide P ₂ bound to a radioactive halogen; wherein,

X includes I, A and F, and n is selected from 20 to 120;

The amino acid sequence of the tail peptide _P2 that binds to the radioactive halogen is selected from the group consisting of YGYGYGYGYGYGY;

The radioactive halogen is selected from ¹²³ I, ¹²⁴ I, ¹²⁵ I, ¹³¹ I.

In some embodiments, the radionuclide is selected ^{from125I or131I} .

In some embodiments, the amino acid sequence of the elastin-like polypeptide _P1 is (VPGXG)n, wherein X is I, A and F, and n is selected from 20 to 120.

Furthermore, n is selected from 50-100.

Furthermore, in the elastin-like polypeptide _P1, X is I, A and F, and the number of amino acids is I:A:F=2:2:1.

Furthermore, the n is 100.

Furthermore, the amino acid sequence of the elastin-like polypeptide _P1 is I ₂₀ A ₂₀ I ₂₀ F ₂₀ A ₂₀ .

Furthermore, the amino acid sequence of the elastin-like polypeptide _P1 is shown in SEQ ID NO: 3,

In some embodiments, the amino acid sequence of the elastin-like polypeptide _P1 is (VPGXG)n, wherein X is I, A, F and L, and n is selected from 20 to 120.

Furthermore, n is selected from 60-120.

Furthermore, the number of amino acids in the elastin-like polypeptide _P1 is I:A:F:L=2:2:1:1.

Furthermore, n is 120.

Furthermore, the amino acid sequence of the elastin-like polypeptide _P1 is I ₂₀ A ₂₀ I ₂₀ F ₂₀ A ₂₀ L ₂₀ .

Furthermore, the amino acid sequence of the elastin-like polypeptide _P1 is shown in SEQ ID NO:4,

In some embodiments, the amino acid sequence of the elastin-like polypeptide _P1 includes a leader peptide.

In some embodiments, the leader peptide is selected from MGSSGLVPRGSKGPG, MSKGPG.

In some embodiments, the amino acid sequence composed of the elastin-like polypeptide _P1 and the tail peptide _P2 also retains the amino acid WP in the SfiI restriction site.

In some embodiments, in order to ensure seamless connection of the amino acid sequence of the elastin-like polypeptide of the present invention, I, A, F and L in the sequence can be replaced by V.

Furthermore, to ensure seamless connection of the sequences, I, A, F or L in the amino acid sequences of SEQ ID NO:3 and SEQ ID NO:4 were independently replaced by V.

Furthermore, to ensure seamless sequence connection, the first I, A, and F of each monomer ELP module in the amino acid sequences of SEQ ID NO:3 and SEQ ID NO:4 were replaced with V.

In some embodiments, the amino acid sequence of the elastin-like polypeptide _P1 and the tail peptide _P2 is as shown in SEQ ID NO: 1 or SEQ ID NO: 2:

In some embodiments, the preparation process of the radionuclide-labeled elastin-like polypeptide comprises:

S1: Preparation of elastin-like polypeptide: overexpression of elastin-like polypeptide in Escherichia coli by induction with IPTG, and then repeating the ITC process to obtain purified elastin-like polypeptide; or synthesis of elastin-like polypeptide by peptide Fmoc synthesis method;

S2: Radioactive iodine labeling: Use the chloramine T (Ch-T) method or the Iodogen (chloroglycoluril) method for labeling.

In some embodiments, the preparation process of the radionuclide-labeled elastin-like polypeptide comprises:

S1: Preparation of elastin-like polypeptide: Overexpress elastin-like polypeptide in BL21 by induction of IPTG, collect bacterial cells and break them, then place them on ice for 30 min, centrifuge at 4°C and take the supernatant, add NaCl to the supernatant to a final concentration of 2 M, and incubate in a 45°C water bath. Centrifuge the turbid supernatant at 40°C, remove the supernatant, and suspend the precipitate in cold PBS. Centrifuge the resulting resuspension at 4°C, collect the supernatant, and repeat the ITC process again to obtain the purified product;

S2: Radioactive iodine labeling: Adjust the ELP concentration to 750μM, add 20μL ELP to the iodogen coated tube, and place on ice. Add 6mCi NaI-125 and 1-2mCi NaI-131 to the iodogen coated tube, respectively, to ensure that the total volume in each tube is 200μL, label the tubes separately, and the total radiation dose is 40mCi. React in a 4℃ constant temperature mixer.

Furthermore, the amino acid sequence of the radionuclide-labeled elastin-like polypeptide is as shown in SEQ ID NO: 1 or SEQ ID NO: 2.

In another aspect, the present invention provides a pharmaceutical composition, comprising the above-mentioned radionuclide-labeled elastin-like polypeptide and a pharmaceutically acceptable carrier.

In another aspect, the present invention provides a kit, comprising the above-mentioned radionuclide-labeled elastin-like polypeptide.

In another aspect, the present invention provides the use of the above-mentioned radionuclide-labeled elastin-like polypeptide or pharmaceutical composition in the preparation of anti-tumor drugs.

In some embodiments, the tumor is selected from at least one of head and neck squamous cell carcinoma, prostate cancer, liver cancer, neuroendocrine tumors, pancreatic tumors, melanoma, and breast cancer.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG1 is a diagram showing the radioactivity retention of the labeled experimental group in Example 2;

FIG2 is a graph showing the changes in tumor volume of mice after administration in Example 2;

FIG3 is a graph showing the weight changes of mice after administration in Example 2;

FIG4 shows the tumor weight of mice at the end of the experiment in Example 2;

FIG. 5 shows the survival time of mice in Example 2.

Specific embodiments

The present invention is further described in detail below in conjunction with specific embodiments. The embodiments of the present invention are only for describing the technical ideas and features of the present invention, rather than for limiting the protection scope of the present invention.

The technical means used in the examples are conventional means well known to those skilled in the art. The polypeptide (ELP) was synthesized by this unit and dissolved in PBS solution. 131-I and 125-I were provided by Jiangsu Huajing Molecular Imaging and Pharmaceutical Research Institute Co., Ltd., and the head and neck squamous cell carcinoma cell line FaDu was provided by Noyan Biotechnology Co., Ltd. FaDu was cultured according to the method in the product manual. Balb/c female nude mice were purchased from Zhejiang Weitong Lihua Experimental Animal Technology Co., Ltd., and the raw materials used were commercially available products.

Example 1 ELP iodine labeling experiment

1. Preparation of ELP

Synthesis of the polypeptide shown in SEQ ID NO:1.

(1) Construction of leader peptide-tail peptide expression plasmid: The NcoⅠ-leader peptide-tail peptide-XhoⅠ sequence, NcoⅠ-MSKGPGWPYGYGYGYGYGYGYN-XhoⅠ, was artificially designed and synthesized, and this sequence was ligated into the pET15b plasmid and verified by restriction endonuclease digestion with NcoⅠ and XhoⅠ and sequencing.

(2) Construction of ELP module plasmid: (VPGIG) ₂₀ , (VPGAG) ₂₀ , and (VPGFG) ₂₀ related DNA sequences were chemically synthesized and ligated to a full length of 370 bp by annealing. NdeⅠ and HindⅢ restriction sites were designed at the 5′ and 3′ ends of the sequences and cloned into pUC18 plasmid. The residues were verified by NdeⅠ and HindⅢ restriction enzyme digestion and sequenced. Then, pUC18-ELP(I ₂₀ )/(A ₂₀ )/(F ₂₀ ) was constructed in sequence.

(3) Construction of pUC18-ELP(I ₂₀ A ₂₀ I ₂₀ F ₂₀ A ₂₀ ) plasmid: pUC18-ELP(F ₂₀ ) was double-digested with PflMI and BglI to recover the target fragment F ₂₀ , and pUC18-ELP(A ₂₀ ) was linearized and dephosphorylated with PflMI. The two fragments were ligated with T4 DNA ligase, and Top10 competent cells were used for transformation. After the plasmid was extracted, it was verified by digestion with NdeⅠ and HindⅢ to successfully construct pUC18-ELP(F ₂₀ A ₂₀ ). The above steps were repeated until pUC18-ELP(I ₂₀ A ₂₀ I ₂₀ F ₂₀ A ₂₀ ) was successfully constructed.

(4) Construction of pET15b-ELP (I ₂₀ A ₂₀ I ₂₀ F ₂₀ A ₂₀ ) expression plasmid: pUC18-ELP was double-digested with PflMI and BglI (I ₂₀ A ₂₀ I ₂₀ F ₂₀ A ₂₀ ), recover the target fragment; treat the leader peptide-tail peptide expression plasmid with SfiⅠ and dephosphorylate, connect the linearized vector with the target fragment using T4 DNA ligase, and transform it into Arctic Express competent medium, extract the plasmid and verify it by NcoⅠ and XhoⅠ restriction enzyme digestion. pET15b-ELP (I ₂₀ A ₂₀ I ₂₀ F ₂₀ A ₂₀ ) was obtained, and its sequence is shown in SEQ ID NO: 1.

(5) Purification: The pET15b-ELP (I ₂₀ A ₂₀ I ₂₀ F ₂₀ A ₂₀ ) plasmid was transformed into Arctic Express and cultured and shaken. 50 μL of bacterial solution was spread on solid culture medium and incubated at 37°C overnight. Then 1 mL of liquid culture medium was added to scrape the bacterial cells and added to TB culture medium and cultured at 37°C until OD ₆₀₀ = 0.6-0.8. IPTG was added to a final concentration of 1 mM and induced at 37°C for 3 h. The bacterial cells were collected by centrifugation at 4°C and 15,000 × g for 15 min, resuspended in 1× PBS (pH 7.4), and shaken at 37°C and 200 rpm for 1.5 h under the action of a disrupting enzyme. After standing on ice for 30 min to cool the components, the supernatant was centrifuged at 4°C and 15,000 × g for 15 min and NaCl was added to the supernatant to a final concentration of 2 M, and the supernatant was incubated in a 45°C water bath for 15 min. The turbid supernatant was centrifuged at 15000×g for 10 min at 40°C, the supernatant was removed, and the precipitate was suspended in cold PBS. The resulting resuspension was centrifuged at 12000 rpm for 10 min at 4°C, the supernatant was collected, and the ITC process was repeated again to obtain the purified product.

The polypeptide shown in SEQ ID NO:2 was synthesized by referring to the synthesis method of the polypeptide shown in SEQ ID NO:1.

2. Endotoxin Level Assessment

Endotoxin levels exceeding the standard can cause hemorrhagic fever and death in the host. Therefore, to ensure that endotoxin does not affect the in vivo stability experiment, this experiment used Endotoxin Removal Beads to remove endotoxin and used horseshoe crab reagent to detect endotoxin limits.

Mix the Endotoxin Removal Beads thoroughly and use a non-pyrogenic pipette to draw 1 mL into the chromatography column to remove the protective solution. Wash with 3 mL of regeneration solution, control the flow rate at 0.25 mL/min, or less than 10 drops per minute, and control the temperature at 2-8°C. Repeat at least twice to ensure that there is no endotoxin in the column. Use 3 mL of balancing solution to balance the inner wall and filler of the column tube, drain, the flow rate is about 0.5 mL/min, the temperature is controlled at 2-8°C, and repeat at least twice. Add the sample to the balanced column, adjust the flow rate to 0.25 mL/min, and start collecting the effluent when about 1 mL of effluent flows out. After draining, add 1 mL of balancing solution and continue collecting. Use horseshoe crab reagent to detect the endotoxin content in the sample (FDA endotoxin standard is 5 EU/dose (1 dose = 1 mg)) to ensure that endotoxin does not exceed the standard. Endotoxin detection levels are shown in Table 1 below:

Table 1 Endotoxin detection levels

The results showed that the endotoxin content in the ELPs sample of the present invention was low, which could ensure the safety of clinical medication. ITC was performed again to concentrate the ELP and measure the protein concentration

3. Radioiodine labeling

Take 20 μL of the polypeptide shown in SEQ ID No: 1 with a concentration of 750 μM in an iodogen-coated tube and place it on ice. Add NaI-125 and NaI-131 to the iodogen-coated tube respectively, the amount of which is shown in Table 2 and Table 3, and mark the experimental groups. Carry out, and ensure that the total volume in each tube is 220μL, and react at 4℃ constant temperature mixer 800rpm for 1h. After the reaction is completed, use a pipette to collect the labeled products and merge them into one tube, and measure the radioactivity after the reaction by a γ counter. Heat in a 30℃ thermostat for 5min until a turbid color is visible in the tube, centrifuge at 30℃1000rpm for 5min, collect the supernatant, and measure the activity of the supernatant and the labeled product, calculate the labeling efficiency, and the labeling efficiency is shown in Table 2 and Table 3, which are 56.96% and 64.91%, respectively, to achieve radioiodine labeling of ELP. Then add the corresponding volume of pre-cooled PBS or unlabeled ELP, rotate at 4℃ until the ELP precipitate dissolves, and adjust the radiation dose to 50μCi/μL or more.

Table 2 NaI-125 labeling system

Table 3 NaI-131 labeling system

Example 2 Animal Experiment

1. Establishment of nude mouse subcutaneous tumor model

The head and neck squamous cell carcinoma cell line FaDu prepared for injection into mice was provided by Noyan Biotech Co., Ltd. and cultured according to the product instructions. FaDu was cultured using complete medium for human pharyngeal squamous cell carcinoma cells supplied by Starfish and cultured in a 95% air + 5% carbon dioxide incubator at 37°C.

Human pharyngeal squamous cell carcinoma cell FaDu cells were cultured to the logarithmic phase, washed twice with pre-cooled PBS, digested with trypsin and collected, washed twice with PBS, and then diluted with PBS to a cell suspension of 1×10 ⁷ cells/mL, and stored in an ice box. The inoculation system for each mouse was 1×10 ⁶ cells/100 μL. 45 female Balb/c-nu athymic nude mice were prepared. When the nude mice were awake, they were placed on the mesh cover of the mouse cage. FaDu cells were inoculated subcutaneously in the right calf of the nude mice with a 1mL syringe. The inoculated animals were observed and their weights were recorded every day. After the animal model was established, the tumor growth status and tumor size were observed once a day. The longest (L) and shortest (W) of the tumor were measured with a vernier caliper. The tumor volume calculation formula = 0.5×L×W ² (mm ³ ). Until the tumor size grew to about 150±20mm ³ .

2. Animal Drug Administration

Female Balb/c-nu athymic nude mice were randomly divided into 3 groups (n=10) according to tumor volume and body weight and a fixed dose of drug (prepared in Example 1) was administered for treatment experiment. The ELP molar concentration of Group 1 was consistent with that of Group 2 and Group 3, as shown in Table 4.

Table 4 Animal dosing grouping

The radiation dose that should be injected for the actual tumor size of athymic nude mice was calculated based on the ratio of 150±20 ^mm3 to 2mCi injection. During the injection, the sterile syringe was placed on ice, the test sample was accurately drawn, the tumor size, the radiation dose and the administration time were recorded, and the injection was directly injected into the tumor. Because ELP has phase change characteristics, there was an obvious oval bulge at the injection site after the injection, indicating that the injected ELP was agglutinated in the tumor, the position was not offset, and the injection was successful. The actual tumor size and injection amount are shown in Table 5.

Table 5 Actual animal tumor size and injection volume

One week before treatment, 1% potassium iodide was added to the drinking water of all animals and continued until the end of the radiotherapy experiment. The mice were monitored daily for tumor radioactivity, tumor volume, body weight (BW), and survival rate in the first week after administration; every other day in weeks 2-4; and twice a week in weeks 5-8 until the end of the experiment. The experiment was terminated until the level of each mouse dropped to less than 5% of the dosing level, the tumor volume reached 5 times the initial tumor volume, and the body weight dropped to less than 85% of the body weight or 77 days after treatment (end of the experiment). The animals were euthanized and grossly dissected, and the tumors were weighed and photographed.

Results: Figure 1 shows the radioactivity retention in the experimental group: The decay half-life of I-131 in the tumor (7.81 days) is comparable to its physical half-life (8.1 days). The stability of I-125 is not as good as expected, only 21.3 days, 2/3 shorter than its physical half-life of 60.

The results in Figure 2-5 show that compared with the ELP-cold drug group, the tumor continued to grow. After the injection of I121-ELP and I131-ELP, the tumor volume no longer increased and tended to decrease, indicating that ELP played the role of a drug reservoir, and radioactive iodine could accurately kill tumor tissue, prevent tumor growth, and increase the survival time of mice; compared with the ELP-cold drug group, the weight of mice in the experimental group did not decrease, indicating that local radiotherapy had no toxic effects on the animal body; after the experiment, the tumor weight was weighed, and the reduction in tumor weight in the experimental group compared with the ELP-cold drug group was statistically significant.

Claims (10)

A radionuclide-labeled elastin-like polypeptide, characterized in that the radionuclide-labeled elastin-like polypeptide structure consists of an elastin-like polypeptide _P1 represented by (VPGXG)n and a) a metal chelator complexed with a metal radionuclide; or consists of an elastin-like polypeptide _P1 represented by (VPGXG)n and b) a tail peptide _P2 combined with a radioactive halogen; wherein, X includes I, A and F, and n is selected from 20 to 120; The metal chelator is selected from DOTA, DTPA, and NOTA; The amino acid sequence of the tail peptide _P2 that binds to the radioactive halogen is selected from the group consisting of YGYGYGYGYGYGY; The radioactive halogen is selected from ¹⁸ F, ¹²³ I, ¹²⁴ I, ¹²⁵ I, ¹³¹ I, ²¹¹ At; The metal radionuclide is selected from ⁶⁴ Cu, ⁶⁷ Cu, ⁶⁸ Ga, ⁸⁹ Zr, ¹⁷⁷ Lu, ⁴⁴ Sc, ¹¹¹ In, ⁹⁰ Y, ^99m Tc, ¹⁵³ Sm, ¹⁵³ Gd, ¹⁵⁵ Gd, ¹⁵⁷ Gd, ²¹³ Bi, ²²³ Ra, ²²⁵ Ac. The radionuclide-labeled elastin-like polypeptide according to claim 1, characterized in that the radionuclide-labeled elastin-like polypeptide structure consists of an elastin-like polypeptide P ₁ represented by (VPGXG)n and a tail peptide P ₂ bound to a radioactive halogen; wherein, X includes I, A and F, and n is selected from 20 to 120; The amino acid sequence of the tail peptide _P2 that binds to the radioactive halogen is selected from the group consisting of YGYGYGYGYGYGY; The radioactive halogen is selected from ¹²³ I, ¹²⁴ I, ¹²⁵ I, ¹³¹ I, Furthermore, the radionuclide is selected from ¹²⁵ I or ¹³¹ I. The radionuclide-labeled elastin-like polypeptide according to claim 1 or 2, characterized in that the amino acid sequence of the elastin-like polypeptide _P1 is (VPGXG)n, wherein X is I, A and F, and n is selected from 20 to 120. The radionuclide-labeled elastin-like polypeptide according to claim 4, characterized in that X in the elastin-like polypeptide _P1 is I, A and F, the number of amino acids is I:A:F=2:2:1, and n is 100; further, the amino acid sequence of the elastin-like polypeptide _P1 is I ₂₀ A ₂₀ I ₂₀ F ₂₀ A ₂₀ . The radionuclide-labeled elastin-like polypeptide according to claim 1 or 2, characterized in that the amino acid sequence of the elastin-like polypeptide _P1 is (VPGXG)n, wherein X is I, A, F and L, and n is selected from 20 to 120. The radionuclide-labeled elastin-like polypeptide according to claim 5, characterized in that the amino acid number of the elastin-like polypeptide _P1 is I:A:F:L=2:2:1:1, and n is 120; further, the amino acid sequence of the elastin-like polypeptide _P1 is I ₂₀ A ₂₀ I ₂₀ F ₂₀ A ₂₀ L ₂₀ . The radionuclide-labeled elastin-like polypeptide according to claim 1 or 2, characterized in that the amino acid sequence of the elastin-like polypeptide _P1 includes a leader peptide, and the leader peptide is selected from MGSSGLVPRGSKGPG and MSKGPG; the amino acid sequence composed of the elastin-like polypeptide _P1 and the tail peptide _P2 also retains the amino acid WP in the Sfi I restriction site. The radionuclide-labeled elastin-like polypeptide according to claim 2, characterized in that the amino acid sequence composed of the elastin-like polypeptide _P1 and the tail peptide _P2 is as shown in SEQ ID NO: 1 or SEQ ID NO: 2:
MSKGPGVGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGV
PGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGVGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGV PGAGVPGAGVPGAGVPGAGVPGAGVPGVGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGV PGIGVPGIGVPGVGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGVGV PGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGWPYGYGYGYGYGYGY(SEQ ID NO:1)、
MSKGPGVGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGV
(SEQ ID NO:2). A pharmaceutical composition, characterized in that the composition comprises the radionuclide-labeled elastin-like polypeptide according to any one of claims 1 to 8 and a pharmaceutically acceptable carrier. Use of the radionuclide-labeled elastin-like polypeptide according to any one of claims 1 to 8 and the pharmaceutical composition according to claim 9 in the preparation of an anti-tumor drug, wherein the tumor is selected from at least one of head and neck squamous cell carcinoma, prostate cancer, liver cancer, neuroendocrine tumor, pancreatic tumor, melanoma, and breast cancer.