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

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 radiolabeled elastin-like polypeptide and its preparation method and application Technical Field

[0001] The present invention relates to the field of biomedicine, and in particular to a radiolabeled elastin-like polypeptide and a preparation method and application thereof. Background Art

[0002] Cancer is a broad spectrum of diseases characterized by multiple genetic mutations, triggered by environmental influences, somatic DNA replication errors, and inherited defects. The phenotype of cancer is the uncontrolled growth of abnormal cells, their unlimited replication, and their invasion of surrounding normal tissues. 85% of cancer patients have solid tumors, and 50% of these patients die from their malignant disease. Tumor metastasis is often the ultimate cause of death, but treatment failure can lead to exacerbated metastases due to loss of control of the primary tumor. Primary tumor control is particularly challenging in the cervix, colon, ovary, and pancreas. Therefore, there is an urgent need for improved treatments for primary tumors. Cancer treatment primarily encompasses traditional surgical procedures, radiotherapy, and chemotherapy. Generally, radiotherapy and chemotherapy target rapidly proliferating cells, but cancer cells are not the only rapidly proliferating cells in the body, and their toxic side effects are common on hematopoietic progenitor cells in the bone marrow and intestinal epithelial cells. Surgery involves removing the tumor itself, which has limited impact on normal tissues, making it difficult to define tumor margins and potentially prohibiting successful surgical resection of metastases that are too small.

[0003] The goal of drug delivery in cancer therapy is to increase intratumoral drug concentration while limiting systemic exposure. Numerous delivery methods have been developed to achieve this goal, including liposomes, micelles, affinity-targeted drugs, and macromolecular carriers. Overcoming the limitations of targeted tumor therapy, the discovery of elastin-like peptides as drug storage materials offers a promising approach for cancer treatment.

[0004] Elastin-like polypeptides (ELPs) are temperature-sensitive biopolymers composed of repeating pentapeptide sequences (Val-Pro-Gly-Xaa-Gly) derived from the hydrophobic domains of mammalian elastin. Elastin-like polypeptides undergo a rapid, reversible phase transition with increasing temperature, also known as the lower critical solution temperature (LTC). Elastin-like polypeptides are soluble in aqueous solutions below their LT. However, above the LT, crosslinking and aggregation between ELP chains render them insoluble and lead to precipitation, transforming them into ordered polymers in aqueous environments. This phase transition is reversible, and the transition temperature can be adjusted by adjusting the type, molecular weight, and concentration of the Xaa residues. Therefore, the LTC can be precisely controlled by adjusting the sequence and length of the ELPs to tailor the drug's characteristics, therapeutic needs, and temporal and spatial drug release and targeting.

[0005] Furthermore, elastin-like proteins can be expressed by fusing them with elastin-like polypeptide sequences through genetic engineering, or by designing corresponding active groups that chemically react with drugs to covalently bind them to elastin-like polypeptide chains, forming ELPs-drug conjugates. Elastin-like polypeptides act as drug carriers to treat a variety of diseases, such as siEVI1-ELP for various cancers (breast, ovarian, pancreatic, and lung), VIP-ELP for pulmonary hypertension, cardiomyopathy, and cystic fibrosis, and GLP1-ELP for type 2 diabetes.

[0006] 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, achieving long-term drug efficacy and local drug delivery.

[0007] The radionuclide-labeled elastin-like polypeptide designed in the present invention can be precisely injected into the tumor. Due to the phase change properties of elastin-like proteins, once it enters the tumor, it can be fixed inside the tumor. The radiation effect of the radionuclide kills cancer cells, thereby causing cancer cell death, accurately eliminating or reducing tumor tissue, and has broad application prospects in biomedical research, drug development and clinical diagnosis.

[0008] Summary of the Invention

[0009] 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.

[0010] To achieve the above objectives, the present invention adopts the following technical solutions.

[0011] In one aspect, 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 composed of an elastin-like polypeptide P1 represented by (VPGXG)n and b) a tail peptide P2 bound to a radioactive halogen; wherein,

[0012] X includes I, A and F, and n is selected from 20 to 120;

[0013] The metal chelating agent is selected from DOTA, DTPA, and NOTA;

[0014] The amino acid sequence of the tail peptide P2 that binds to the radioactive halogen is selected from the group consisting of YGYGYGYGYGYGY;

[0015] The radioactive halogen is selected from18 F. 123 I. 124 I. 125 I. 131 I. 211 At;

[0016] Metal radionuclides are 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.

[0017] 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,

[0018] X includes I, A and F, and n is selected from 20 to 120;

[0019] The metal chelating agent is selected from DOTA, DTPA, and NOTA;

[0020] Metal radionuclides are 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.

[0021] In some embodiments, the radionuclide-labeled elastin-like polypeptide structure consists of an elastin-like polypeptide P1 represented by (VPGXG)n and a tail peptide P2 bound to a radioactive halogen; wherein,

[0022] X includes I, A and F, and n is selected from 20 to 120;

[0023] The amino acid sequence of the tail peptide P2 that binds to the radioactive halogen is selected from the group consisting of YGYGYGYGYGYGY;

[0024] The radioactive halogen is selected from 123 I. 124 I. 125 I. 131 I.

[0025] In some embodiments, the radionuclide is selected from 125 I or 131 I.

[0026] 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.

[0027] Furthermore, n is selected from 50 to 100.

[0028] 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.

[0029] Furthermore, the n is 100.

[0030] Furthermore, the amino acid sequence of the elastin-like polypeptide P1 is 20 A 20 I 20 F 20 A 20 .

[0031] Furthermore, the amino acid sequence of the elastin-like polypeptide P1 is shown in SEQ ID NO: 3,

[0032] 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.

[0033] Furthermore, n is selected from 60 to 120.

[0034] Furthermore, the amino acid number of the elastin-like polypeptide P1 is I:A:F:L=2:2:1:1.

[0035] Furthermore, n is 120.

[0036] Furthermore, the amino acid sequence of the elastin-like polypeptide P1 is 20 A 20 I 20 F20 A 20 L 20 .

[0037] Furthermore, the amino acid sequence of the elastin-like polypeptide P1 is shown in SEQ ID NO: 4,

[0038] In some embodiments, the amino acid sequence of the elastin-like polypeptide P1 includes a leader peptide.

[0039] In some embodiments, the leader peptide is selected from MGSSGLVPRGSKGPG, MSKGPG.

[0040] In some embodiments, the amino acid sequence composed of the elastin-like polypeptide P1 and the tail peptide P2 further retains the amino acid WP in the SfiI cleavage site.

[0041] 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.

[0042] Furthermore, to ensure seamless sequence connection, I, A, F or L in the amino acid sequences of SEQ ID NO: 3 and SEQ ID NO: 4 are each independently replaced by V.

[0043] 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.

[0044] 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:

[0045] In some embodiments, the process for preparing the radionuclide-labeled elastin-like polypeptide comprises:

[0046] S1: Preparation of elastin-like polypeptide: Overexpression of elastin-like polypeptide in Escherichia coli by induction with IPTG, followed by repeated ITC process to obtain purified elastin-like polypeptide; or synthesis of elastin-like polypeptide by peptide Fmoc synthesis method;

[0047] S2: Radioactive iodine labeling: Chloramine T (Ch-T) method or Iodogen (chloroglycoluril) method is used for labeling.

[0048] In some embodiments, the process for preparing the radionuclide-labeled elastin-like polypeptide comprises:

[0049] S1: Preparation of elastin-like polypeptide: Overexpress elastin-like polypeptide in BL21 cells using IPTG induction. Collect and disrupt bacterial cells, incubate on ice for 30 minutes, centrifuge at 4°C, and remove 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 resuspend the precipitate in chilled PBS. Centrifuge the resulting resuspension at 4°C, collect the supernatant, and repeat the ITC process to obtain the purified product.

[0050] S2: Radioiodine Labeling: Adjust the ELP concentration to 750 μM. Add 20 μL of ELP to an iodogen-coated tube and place on ice. Add 6 mCi of NaI-125 and 1–2 mCi of NaI-131 to each iodogen-coated tube, ensuring a total volume of 200 μL. Label each tube separately for a total radioiodine dose of 40 mCi. Incubate the tubes at 4°C in a thermomixer.

[0051] Furthermore, the amino acid sequence of the radionuclide-labeled elastin-like polypeptide is shown in SEQ ID NO: 1 or SEQ ID NO: 2.

[0052] In another aspect, the present invention provides a pharmaceutical composition comprising the radionuclide-labeled elastin-like polypeptide and a pharmaceutically acceptable carrier.

[0053] In another aspect, the present invention provides a kit comprising the above-mentioned radionuclide-labeled elastin-like polypeptide.

[0054] In another aspect, the present invention provides use of the radionuclide-labeled elastin-like polypeptide or pharmaceutical composition in the preparation of anti-tumor drugs.

[0055] In some embodiments, 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. BRIEF DESCRIPTION OF THE DRAWINGS

[0056] FIG1 shows the radioactivity retention of the labeled experimental group in Example 2;

[0057] FIG2 is a graph showing changes in tumor volume in mice after administration of the drug in Example 2;

[0058] FIG3 is a graph showing changes in body weight of mice after administration in Example 2;

[0059] FIG4 shows the tumor weight of mice at the end of the experiment in Example 2;

[0060] FIG5 shows the survival time of mice in Example 2. Specific embodiments

[0061] The present invention will be further described in detail below with reference to specific embodiments. The embodiments of the present invention are only for illustrating the technical ideas and features of the present invention, and are not intended to limit the scope of protection of the present invention.

[0062] The techniques used in the examples are conventional methods well known to those skilled in the art. The polypeptide (ELP) was synthesized in-house and dissolved in PBS. 131-I and 125-I were provided by Jiangsu Huajing Molecular Imaging and Pharmaceutical Research Institute Co., Ltd. The head and neck squamous cell carcinoma cell line FaDu was provided by Noyan Biotechnology Co., Ltd. and cultured according to the product instructions. Balb / c female nude mice were purchased from Zhejiang Weitong Lihua Laboratory Animal Technology Co., Ltd. All raw materials used were commercially available products.

[0063] Example 1 ELP iodine labeling experiment

[0064] 1. Preparation of ELP

[0065] Synthesis of the polypeptide shown in SEQ ID NO: 1.

[0066] (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 enzyme digestion with NcoⅠ and XhoⅠ and sequencing.

[0067] (2) ELP module plasmid construction: chemical synthesis (VPGIG) 20 、(VPGAG) 20 、(VPGFG) 20 The relevant DNA sequence was annealed to the full length of 370 bp, and NdeⅠ and HindⅢ restriction sites were designed at the 5′ and 3′ ends of the sequence, and cloned into the pUC18 plasmid. The NdeⅠ and HindⅢ restriction enzyme sites were verified and sequenced, and the pUC18-ELP(I 20 ) / (A 20 ) / (F 20 ).

[0068] (3)pUC18-ELP(I 20 A 20 I 20 F 20 A 20 ) Plasmid construction: pUC18-ELP (F20 ), recover the target fragment F 20 , PflMI single enzyme digestion linearized pUC18-ELP (A 20 ) and dephosphorylated, the two were connected by T4 DNA ligase, Top10 competent cells were transformed, and the plasmid was extracted and verified by NdeⅠ and HindⅢ enzyme digestion. The pUC18-ELP (F 20 A 20 Repeat the above steps until pUC18-ELP(I 20 A 20 I 20 F 20 A 20 ).

[0069] (4) pET15b-ELP(I 20 A 20 I 20 F 20 A 20 ) Expression plasmid construction: pUC18-ELP (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 it, connect the linearized vector with the target fragment using T4 DNA ligase, and transform it into Arctic Express competent medium. After extracting the plasmid, NcoⅠ and XhoⅠ enzyme digestion were used for verification. 20 A 20 I 20 F 20 A 20 ), the sequence of which is shown in SEQ ID NO: 1.

[0070] (5) Purification: pET15b-ELP(I 20 A 20 I 20 F 20 A 20 ) plasmid was transformed into Arctic Express and cultured by shaking. 50 μL of bacterial solution was spread on solid culture medium and incubated at 37°C overnight. 1 mL of liquid culture medium was added to scrape the bacterial cells and added to TB medium and cultured at 37°C until OD 600=0.6-0.8. Add IPTG to a final concentration of 1 mM, induce culture at 37°C for 3 hours, collect bacterial cells by centrifugation at 4°C 15000×g for 15 minutes, resuspend in 1×PBS (pH 7.4), and shake at 37°C 200rpm for 1.5 hours under the action of a disrupting enzyme. After standing on ice for 30 minutes to cool the components, centrifuge at 4°C 15000×g for 15 minutes and take the supernatant. Add NaCl to the supernatant to a final concentration of 2M and incubate in a 45°C water bath for 15 minutes. Centrifuge the turbid supernatant at 40°C 15000×g for 10 minutes, remove the supernatant, and suspend the precipitate in cold PBS. Centrifuge the resulting resuspension at 4°C 12000rpm for 10 minutes, collect the supernatant, and repeat the ITC process again to obtain the purified product.

[0071] 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.

[0072] 2. Endotoxin Level Assessment

[0073] 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 uses Endotoxin Removal Beads to remove endotoxins and uses Limulus amebocyte lysate to detect endotoxin limits.

[0074] Mix the Endotoxin Removal Beads thoroughly and use a pyrogen-free pipette tip to draw 1 mL into the chromatography column to remove the protective liquid. 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 equilibrium solution to balance the inner wall of the column tube and the filler, 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 equilibrium solution and continue collecting. Use Limulus amebocyte lysate 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. The endotoxin detection level is as shown in Table 1 below:

[0075] Table 1 Endotoxin detection levels

[0076] The results showed that the endotoxin content in the ELPs sample of the present invention was low, which can ensure the safety of clinical medication. ITC was performed again to concentrate the ELP and measure the protein concentration.

[0077] 3. Radioiodine labeling

[0078] 20 μL of the polypeptide represented by SEQ ID No: 1 at a concentration of 750 μM was placed in an iodogen-coated tube and placed on ice. NaI-125 and NaI-131 were added to the iodogen-coated tubes, respectively, in the amounts shown in Tables 2 and 3. Labeling experiments were performed in groups, ensuring a total volume of 220 μL in each tube. The reaction was performed in a 4°C thermomixer at 800 rpm for 1 hour. After the reaction, the labeled products were pipetted and combined into a single tube. The post-reaction radioactivity was measured using a gamma counter. The tubes were heated in a 30°C thermostat for 5 minutes until turbidity appeared. The supernatant was centrifuged at 30°C and 1000 rpm for 5 minutes. The supernatant was collected and the activity of the supernatant and labeled products was measured. The labeling efficiency was calculated. As shown in Tables 2 and 3, the labeling efficiencies were 56.96% and 64.91%, respectively, demonstrating radioiodine labeling of ELP. Then, the corresponding volume of pre-chilled PBS or unlabeled ELP was added and rotated at 4°C until the ELP precipitate dissolved. The radiation dose was adjusted to 50 μCi / μL or above.

[0079] Table 2 NaI-125 labeling system

[0080] Table 3 NaI-131 labeling system

[0081] Example 2 Animal Experiment

[0082] 1. Establishment of Nude Mouse Subcutaneous Tumor Model

[0083] FaDu, a head and neck squamous cell carcinoma cell line, was prepared for injection into mice. It was provided by Noyan Biotech Co., Ltd. and cultured according to the product instructions. FaDu cells were cultured using Starfish complete medium for human pharyngeal squamous cell carcinoma cells in a 95% air + 5% carbon dioxide incubator at 37°C.

[0084] Human pharyngeal squamous cell carcinoma 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 Each mouse was inoculated with 1×10 6 Forty-five female Balb / c-nu athymic nude mice were prepared. The mice were awake and placed on the cage mesh cover. FaDu cells were inoculated subcutaneously into the right calf of the mice using a 1 mL syringe. The status of the inoculated animals was observed and the weight was recorded daily. After the animal model was established, the tumor growth status and tumor size were observed once a day. The longest (L) and shortest (W) lengths of the tumors were measured using a vernier caliper. The tumor volume was calculated using the formula = 0.5 × L × W 2 (mm 3). Until the tumor size grows to 150±20mm 3 about.

[0085] 2. Animal Dosing

[0086] Female Balb / c-nu athymic nude mice were randomly divided into 3 groups (n=10) based on tumor volume and body weight and were given a fixed dose of the drug (prepared in Example 1) for treatment. The ELP molar concentrations in Group 1 were consistent with those in Groups 2 and 3, as shown in Table 4.

[0087] Table 4 Animal dosing grouping

[0088] According to 150±20mm 3 The radiation dose required to inject 2 mCi was calculated based on the actual tumor size in athymic nude mice. During injection, the sterile syringe was placed on ice, and the test sample was accurately drawn. The tumor size, dose, and time of administration were recorded, and the injection was directly into the tumor. Due to the phase transition properties of ELP, a distinct elliptical bulge was observed at the injection site after injection, indicating that the injected ELP had accumulated within the tumor without displacement, indicating a successful injection. The actual tumor size and injection dose are shown in Table 5.

[0089] Table 5 Actual animal tumor size and injection volume

[0090] 1% potassium iodide was added to the drinking water of all animals one week before treatment 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 dosed 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 the tumors were removed for weighing and photographing.

[0091] Results: Figure 1 shows the radioactivity retention in the experimental group: The decay half-life of I-131 in the tumor (7.81 days) was comparable to its physical half-life (8.1 days). The stability of I-125 was less stable than expected, at only 21.3 days, two-thirds shorter than its physical half-life of 60 days.

[0092] The results in Figures 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, suggesting that local radiotherapy had no toxic effects on the animal body; after the end of 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

1. A radionuclide-labeled elastin-like polypeptide, characterized in that: The radionuclide-labeled elastin-like polypeptide structure is composed of the elastin-like polypeptide P1 shown in (VPGXG)n and a) a metal chelator complexed with a metal radionuclide; or is composed of the elastin-like polypeptide P1 shown in (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 radionuclides are 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.

2. The radionuclide-labeled elastin-like polypeptide according to claim 1, characterized in that: The radionuclide labeled elastin-like polypeptide structure is composed of an elastin-like polypeptide P1 represented by (VPGXG)n and 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 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.

3. 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.

4. The radionuclide-labeled elastin-like polypeptide according to claim 4, characterized in that: In the elastin-like polypeptide P1, X 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 .

5. 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.

6. 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 .

7. 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 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.

8. 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 PGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGVGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGVGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGVGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGFGVPGVGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGAGVPGWPYGYGYGYGYGYGY(SEQ ID NO:1), MSKGPGVGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGVPGIGV(SEQ ID NO:2).

9. 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.

10. 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 anti-tumor drugs, wherein 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.

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