Pancreatic cancer specific binding peptide and preparation method and application thereof
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- BEIJING BEISHENG BIOTECHNOLOGY CO LTD
- Filing Date
- 2026-04-01
- Publication Date
- 2026-06-23
AI Technical Summary
Existing targeted drugs for CLDN18.2 are mainly concentrated in the field of monoclonal antibodies, which have problems such as large molecular weight, limited tissue penetration, high production cost and potential immunogenicity. There is a lack of peptide molecules that specifically and have high affinity to bind to CLDN18.2.
Chelating agent-mediated radiolabeled HFL2c peptides, including imaging radionuclide 68Ga-DOTA-HFL2c and therapeutic radionuclide 177Lu-DOTA-HFL2c, were designed and prepared. The peptides were prepared by solid-phase synthesis and extraction column purification to achieve high affinity binding to CLDN18.2.
It achieves precise localization, quantitative monitoring, and high-sensitivity in vivo imaging of CLDN18.2, making it suitable for early screening and diagnosis of pancreatic cancer. It also has good biocompatibility and safety, and can inhibit the growth of pancreatic cancer tumors.
Smart Images
Figure CN122255229A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of biomedical technology, specifically relating to a pancreatic cancer-specific binding peptide, its preparation method, and its application. Background Technology
[0002] Pancreatic cancer is a highly malignant tumor with an extremely poor prognosis. Most patients are diagnosed at an advanced stage, missing the optimal window for surgery. Therefore, developing effective strategies for early screening, precise diagnosis, and targeted therapy is crucial for improving the survival rate of pancreatic cancer patients.
[0003] In recent years, with the deepening research on tumor molecular markers, members of the tight junction protein CLDN18 family, especially its isoform CLDN18.2, have shown unique application value. As a key transmembrane protein maintaining tight junctions between epithelial cells, CLDN18.2 exhibits specific high expression on pancreatic cancer cell membranes, while its distribution is restricted in normal tissues. This expression characteristic makes it an ideal tumor-specific target. Genomic analysis further confirms that the expression level of CLDN18.2 is closely related to the prognosis of pancreatic cancer patients, highlighting its dual potential as a diagnostic marker and therapeutic target.
[0004] Currently, the development of targeted drugs for CLDN18.2 mainly focuses on monoclonal antibodies, and some clinical progress has been made. However, antibody drugs suffer from problems such as large molecular weight, limited tissue penetration, high production costs, and potential immunogenicity. In contrast, peptide drugs have unique advantages such as small molecular weight, strong tissue penetration, relatively simple synthesis processes, ease of chemical modification, and low immunogenicity, showing great potential in tumor diagnostic imaging and targeted delivery.
[0005] Nevertheless, there are still few reports, both domestically and internationally, on high-affinity peptide molecules targeting pancreatic cancer, particularly those specifically targeting CLDN18.2. Therefore, there is an urgent need to design and develop a peptide molecule that can specifically and with high affinity bind to the CLDN18.2 target, providing a new solution for precision medicine of pancreatic cancer. Summary of the Invention
[0006] The primary objective of this invention is to provide a pancreatic cancer-specific binding peptide.
[0007] The second objective of this invention is to provide a method for preparing a pancreatic cancer-specific binding peptide.
[0008] A third objective of this invention is to provide the use of a pancreatic cancer-specific binding peptide in the preparation of targeted drugs for the treatment or diagnosis of pancreatic cancer.
[0009] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A pancreatic cancer-specific binding peptide, wherein the pancreatic cancer-specific binding peptide is a chelating agent-mediated radionuclide-labeled HFL2c peptide; wherein the radionuclide includes imaging radionuclides or therapeutic radionuclides; the amino acid sequence of the HFL2c peptide is shown in SEQ ID NO. 1.
[0010] Furthermore, the chelating agent is DOTA.
[0011] Furthermore, the imaging radionuclide is 68 Ga; the therapeutic radionuclide is 177 Lu.
[0012] The preparation method of the pancreatic cancer-specific binding peptide described above specifically includes the following steps: (1) Dissolve the HFL2c peptide coupled with the chelating agent in sodium acetate buffer to obtain a mixed solution, and then add 68 Mix the GaCl3 solution and adjust the pH to 3.5-4.5; heat at 90-95℃ for 8-12 minutes to obtain the reaction solution; (2) The reaction solution obtained in step (1) was purified by C18 solid phase extraction column, washed with water, and then eluted with 50-70% (v / v) ethanol aqueous solution to obtain HFL2c peptide labeled with chelating agent-mediated imaging radionuclides.
[0013] Furthermore, the preparation method specifically includes the following steps: (1) The HFL2c peptide coupled with the chelating agent and the free radical scavenger were mixed in ammonium acetate buffer to obtain a mixed solution, and then added 177 Mix with LuCl3 solution, adjust pH to 4.8-5.5; heat at 85-95℃ for 20-30 min to obtain reaction solution; (2) The reaction solution obtained in step (1) is purified by C18 solid phase extraction column, washed with water, and then eluted with 40-60% (v / v) ethanol aqueous solution to obtain chelating agent-mediated therapeutic radionuclide-labeled HFL2c peptide.
[0014] Further, the concentration of the sodium acetate buffer solution is 0.2-0.3 M; the concentration of the HFL2c peptide conjugated with the chelating agent in the mixed solution is 18-22 μg / mL; the mixed solution and 68 The volume ratio of the GaCl3 solution is 1:1.
[0015] Further, the concentration of the ammonium acetate buffer is 0.1-0.2 M; the concentration of the HFL2c peptide conjugated with the chelating agent in the mixed solution is 18-22 μg / mL; the free radical scavenger is gentianic acid, and its concentration in the ammonium acetate buffer is 10 mg / mL; the mixed solution and 177 The volume ratio of the LuCl3 solution is 2:1.
[0016] The above describes the application of a pancreatic cancer-specific binding peptide in the preparation of targeted drugs for the treatment or diagnosis of pancreatic cancer.
[0017] Compared with the prior art, the main advantages of the present invention are: This invention provides a pancreatic cancer-specific binding peptide, HFL2c, with the amino acid sequence shown in SEQ ID NO. 1: Arg-Glu-Val-Ala-Glu-Ala-Asp-Leu-Ser-Ala-Ala-Ile-Ser-Ala-Lys-Pro-Leu-Gln-Arg-Trp-Glu-Leu-Arg. Experimental results show that this HFL2c peptide can target and bind to the extracellular region of CLDN18.2. The imaging-grade radionuclide-labeled HFL2c peptide prepared using this peptide can be used for radionuclide imaging, enabling precise localization, quantitative monitoring, and high-sensitivity in vivo imaging of CLDN18.2 expression, suitable for early screening, diagnosis, and treatment monitoring of pancreatic cancer. Simultaneously, the therapeutic radionuclide-labeled HFL2c peptide prepared using this peptide can inhibit pancreatic cancer tumor growth. Furthermore, this peptide exhibits good biocompatibility and safety, is readily available, and easy to promote, showing broad application prospects. Attached Figure Description
[0018] Figure 1 The results of the structural analysis of the CLDN18.2 target and the rational design analysis of the HFL2c targeting peptide are shown below; (A) shows the structure of CLDN18.2; (B) shows the binding of the CLDN18.2 short peptide radiopharmaceutical to the extracellular region; (C) shows the protein sequence of the CLDN18.2 short peptide radiopharmaceutical; and (D) shows the surface electrostatic potential energy of the CLDN18.2 short peptide radiopharmaceutical binding to the extracellular region. Figure 2 for 68 In vivo targeting specificity and imaging contrast of Ga-DOTA-HFL2c against CLDN18.2-positive tumors; (A) shows the results of inoculation of CLDN18.2-positive and negative tumors in immunodeficient mice. (B) shows the radionuclide uptake in the CLDN18.2-positive and negative groups; Figure 3 for 68In vivo uptake intensity of Ga-DOTA-HFL2c and expression level of CLDN18.2 protein in tumor tissue; (A) histochemical staining of pancreatic cancer tissue; (B) radionuclide imaging; (C) radionuclide uptake of low, medium and high expression of CLDN18.2. Figure 4 The figure shows the effect of a pancreatic cancer-specific binding peptide on the body weight of tumor-bearing mice. Figure 5 This figure shows the effect of a pancreatic cancer-specific binding peptide on the volume of subcutaneous xenografts in tumor-bearing mice. Detailed Implementation
[0019] The following is a further detailed description of the present invention in conjunction with specific preferred embodiments, and it should not be construed that the specific implementation of the present invention is limited to these descriptions. For those skilled in the art, various simple deductions or substitutions can be made without departing from the concept of the present invention, and all such modifications and substitutions should be considered within the scope of protection of the present invention. Specific conditions not specified in the embodiments are performed according to conventional conditions or conditions recommended by the manufacturer. Unless otherwise specified, all reagents or instruments used are conventional products obtained through commercial channels.
[0020] Example 1 HFL2c targeting peptide design based on CLDN18.2 protein structure To obtain a high-affinity short peptide that can specifically target CLDN18.2, we first analyzed the extracellular structure of CLDN18.2. Figure 1 The potential epitope information of CLDN18.2 was identified. Based on this structure, molecular docking and virtual screening were performed using a computer simulation platform, and a series of candidate peptide sequences were designed and generated targeting its extracellular region. By systematically evaluating the binding free energy, complex conformational stability, and key interactions of each candidate sequence with CLDN18.2, the core sequence with high theoretical affinity was finally screened out and named HFL2c. The amino acid sequence of the HFL2c peptide is shown in SEQ ID NO. 1. SEQ ID NO. 1: Arg-Glu-Val-Ala-Glu-Ala-Asp-Leu-Ser-Ala-Ala-Ile-Ser-Ala-Lys-Pro-Leu-Gln-Arg-Trp-Glu-Leu-Arg; Computer simulations show that the peptide can stably bind to the extracellular region of CLDN18.2 in the predicted model. Figure 1 (B), the amino acid sequence of this polypeptide is as follows: Figure 1As shown in Figure C. Further analysis of the molecular surface electrostatic potential revealed that the electrostatic potential distribution of the designed short peptide exhibited good complementarity with the electrostatic potential of the CLDN18.2 target binding pocket. Figure 1 (D), which theoretically explains the physicochemical basis of its specific binding, providing a key basis for subsequent chemical synthesis and functional verification.
[0021] Example 2 Preparation of the peptide-chelating agent conjugate DOTA-HFL2c The preparation method of the peptide-chelating agent conjugate DOTA-HFL2c specifically includes the following steps: (1) Place Rink Amide-AM Resin in the solid phase synthesis tube of the peptide synthesizer, add 8 times the resin volume of DMF to swell for 25 min, and then dry.
[0022] (2) Add 10 times the resin volume of 20v / v% piperidine and react for 15 min to remove the Fmoc protecting group. Wash 6 times with 9 times the resin volume of DMF. The resin is positive for ninhydrin detection.
[0023] (3) Take the first amino acid FMOC-Arg(Pbf)-OH at the C-terminus, add it together with DIC and HOBT into the synthesizer, and perform a condensation reaction for 52 min. Wash the resin with DMF, and test the resin with ninhydrin. If the resin is negative, proceed with the conjugation of the next amino acid. The ratio of Fmoc-Arg(Pbf)-OH, DIC and HOBT is 3 mmol: 3 mmol: 3 mmol.
[0024] (4) Repeat steps (2) and (3) to sequentially combine the SEQ ID NO.1 sequence from the C-terminus to the N-terminus in the synthesizer according to the predetermined amino acid sequence in SEQ ID NO.1.
[0025] (5) Add 20 v / v% piperidine / DMF solution to remove the terminal Fmoc protecting group, react for 15 min, wash with DMF 6 times, and the ninhydrin test is positive; then add DOTA, HBTU and DIEA for coupling reaction, and the ninhydrin test of the resin is negative; the ratio of DOTA, HBTU and DIEA is 1.0 mmol: 1.2 mmol: 2.0 mmol.
[0026] (6) After coupling, the residual liquid was dried, washed with DCM and vacuum dried, and the cutting solution was added and reacted at room temperature for 3 hours. The cutting solution was a mixed solution of trifluoroacetic acid, triisopropylsilane and water in a volume ratio of 95:2.5:2.5. The solution was filtered, and the filtrate was precipitated with 10 times the volume of diethyl ether. The precipitate was collected by centrifugation to obtain crude HFL2c peptide.
[0027] (7) The crude polypeptide obtained was purified by reversed-phase high-performance liquid chromatography and freeze-dried to obtain the dried high-purity pancreatic cancer-specific binding peptide DOTA-HFL2c.
[0028] Example 3 68 Preparation of Ga-DOTA-HFL2c (1) Take the DOTA-HFL2c powder prepared in Example 2, dissolve it in 0.25 M sodium acetate buffer (pH 4.0) to prepare a mixed solution of 20 μg / mL. Take 1.0 mL of the mixed solution and place it in a reaction flask, add... 68 1.0 mL of GaCl3 solution 68 The GaCl3 solution had a radioactivity concentration of 300 MBq / mL; vortex mixing for 10 seconds. Adjust the pH of the reaction system to 4.0 with 1 M NaOH or ammonia. Place the reaction flask in a 95°C metal heating block and heat for 10 minutes to obtain the reaction solution.
[0029] (2) After cooling the reaction solution obtained in step (1) to room temperature, transfer it to a C18 solid-phase extraction column pre-activated with 5 mL of ethanol and 10 mL of water for purification. First, rinse with 10 mL of ultrapure water to remove unlabeled free ions and water-soluble impurities, and discard the eluent; then elute the target product with 1.0 mL of 70% (v / v) ethanol aqueous solution, and collect the eluent. Dilute the eluent to 10 mL with physiological saline, filter through a 0.22 μm sterile filter membrane, and obtain... 68 Ga-DOTA-HFL2c injection.
[0030] Example 4 177 Preparation of Lu-DOTA--HFL2c (1) Take the DOTA-HFL2c powder prepared in Example 2 and dissolve it in 0.1 M ammonium acetate buffer (pH 5.0) containing 10 mg / mL gentianic acid to prepare a mixed solution of 20 μg / mL. Place 1.0 mL of the mixed solution in a 5 mL borosilicate glass reaction flask and add... 177 0.5 mL of LuCl3 solution, 177 The radioactive concentration of the LuCl3 solution was 600 MBq / mL, and the mixture was vortexed for 30 seconds. The pH of the reaction system was adjusted to 5.0 with 1 M NaOH or 1 M HCl. The reaction flask was placed in a 90°C metal heating module and heated for 25 min to obtain the reaction solution.
[0031] (2) After cooling the reaction solution obtained in step (1) to room temperature, transfer it to a C18 solid-phase extraction column pre-activated with 5 mL of anhydrous ethanol and 10 mL of ultrapure water for purification. First, rinse with 10 mL of ultrapure water to remove unlabeled free ions, gentian acid, and water-soluble impurities, and discard the eluent; then elute the target product with 1.0 mL of 60% (v / v) ethanol aqueous solution and collect the eluent. Dilute the eluent to 10 mL with physiological saline and filter through a 0.22 μm sterile filter membrane to obtain the final product. 177 Lu-DOTA--HFL2c injection.
[0032] Experimental Example 1 To verify the developer 68 The in vivo targeting specificity and imaging contrast of Ga-DOTA-HFL2c against CLDN18.2-positive tumors were evaluated to assess its potential value as a diagnostic probe for CLDN18.2-positive pancreatic cancer. The specific experimental steps are as follows: (1) Human pancreatic cancer cells SW1990 with stable high expression of CLDN18.2 (as positive cells) and isogenetic control cells with CLDN18.2 knocked out using CRISPR-Cas9 technology (as negative cells) were selected. Six- to eight-week-old female BALB / c nude mice were selected as experimental animals, and CLDN18.2 positive cells (5 × 10⁻⁶ cells) were subcutaneously inoculated into their right shoulder. 6 (each tumor cell / animal) was inoculated with an equal amount of CLDN18.2 negative cells in the left shoulder to construct a bilateral control tumor model. The results are as follows: Figure 2 As shown in (A).
[0033] (2) When the bilateral tumors grow to 100-150 mm 3 At that time, the imaging agent was injected via the tail vein. 68 Ga-DOTA-HFL2c injection (prepared in Example 3) was administered as follows: 100 μL per mouse, with an injection activity of 130 μCi per mouse. Small animal PET / CT imaging scans were performed 1 hour post-injection. After image acquisition, three-dimensional volumes of interest were delineated in the bilateral tumor regions using image analysis software, and standardized uptake values (SUVs) were calculated to quantify and compare the uptake differences between the two tumors. The results are as follows: Figure 2 As shown in (B).
[0034] Micro-PET / CT imaging results ( Figure 2 (A) shows that the radioactive signal specifically concentrates at the right CLDN18.2 positive tumor site, while the radioactive uptake of the left negative tumor is not significantly different from the surrounding muscle background, directly demonstrating the targeting specificity of the probe. Quantitative analysis of ex vivo gamma counting (…) Figure 2Further analysis (B) confirmed that the radioactive uptake of CLDN18.2 positive tumors was significantly higher than that of CLDN18.2 negative tumors. This result provides crucial preclinical experimental evidence for its development as a PET imaging agent for the clinical diagnosis and patient screening of CLDN18.2 positive pancreatic cancer.
[0035] Experimental Example 2 In order to evaluate 68 The correlation between the in vivo uptake intensity of Ga-DOTA-HFL2c and the expression level of CLDN18.2 protein in tumor tissue was investigated to verify its potential as a non-invasive imaging biomarker. The specific experimental steps are as follows: (1) Fresh specimens from 35 pancreatic cancer patients were collected, aseptically prepared into tissue blocks, and transplanted subcutaneously into humanized mice to construct a human tumor xenograft (PDX) model library. Simultaneously, CLDN18.2 immunohistochemical staining was performed on paraffin sections of tumor tissue from the corresponding original patients in 35 cases. After scanning the stained sections using a digital pathology system, the CLDN18.2 expression level of each sample was independently assessed using a semi-quantitative H-score scoring method. Based on the scoring results, the PDX models were divided into high, medium, and low expression groups.
[0036] (2) The tumors in the PDX model tumor-bearing mice grew to approximately 200 mm. 3 At that time, the imaging agent was injected via the tail vein. 68 Ga-DOTA-HFL2c injection (prepared in Example 3) was administered as follows: 100 μL per mouse, with an injection activity of 130 μCi, followed by Micro-PET / CT imaging. The tumor region was delineated using image analysis software, and the average standardized uptake value was calculated. Pearson linear regression analysis was used, with the CLDN18.2 IHC score (H-score) of the tumor tissue as the independent variable and the SUV measured by in vivo imaging as the dependent variable, to assess the correlation between the two.
[0037] The results are as follows Figure 3 As shown, 68 The in vivo uptake intensity of Ga-DOTA-HFL2c and the expression level of CLDN18.2 protein in tumor tissue; among which Figure 3 Image A shows representative immunohistochemical staining images of tumor tissues from patients corresponding to different CLDN18.2 expression levels in PDX models. Figure 3 Figure B shows representative Micro-PET / CT images of the corresponding model, visually demonstrating a consistent trend between the imaging agent uptake intensity and IHC staining intensity. Quantitative analysis results ( Figure 3(C) The results showed that the CLDN18.2 IHC score in tumor tissue was significantly positively correlated with in vivo uptake (SUV). That is, the higher the expression level of CLDN18.2 in immunohistochemistry, the higher the radioactive uptake of the probe by the corresponding PDX model, proving... 68 Ga-DOTA-HFL2c PET imaging can non-invasively and quantitatively monitor the expression level of CLDN18.2 in tumors, providing reliable imaging evidence for clinical patient screening and efficacy evaluation.
[0038] Experimental Example 3 Pharmacodynamic evaluation of a pancreatic cancer-specific binding peptide This experiment aims to systematically evaluate 177 The in vivo tumor-suppressive effect of Lu-DOTA-HFL2c on CLDN18.2-positive pancreatic cancer was evaluated by monitoring changes in body weight and tumor volume in tumor-bearing mice to comprehensively assess its therapeutic efficacy and safety. The specific experimental steps are as follows: (1) Human pancreatic cancer cells with high CLDN18.2 expression were selected as the experimental group, and isogenetic cells with CLDN18.2 knocked out using CRISPR-Cas9 technology were used as the control group. Six- to eight-week-old female BALB / c nude mice were selected and divided into two groups: a CLDN18.2 high-expression experimental group and a CLDN18.2 low-expression control group, with six mice in each group. The two cell lines (5 × 10⁻⁶ cells / mL) were subcutaneously inoculated into the right back of both groups of mice. 6 (each tumor cell), until the tumor volume grows to 180-220 mm. 3 When necessary, administer medication.
[0039] (2) Both groups received a single injection via the tail vein. 177 Lu-DOTA-HFL2c injection (prepared in Example 4) was administered as follows: 100 μL per mouse, with an injection activity of 150 μCi per mouse. Starting from the first day of administration, the mice were weighed on days 1, 3, 5, 7, 9, 11, 13, and 15. The results are as follows... Figure 4 As shown. The maximum major diameter (a) and the vertical minor diameter (b) of the tumor were measured every two days using calipers, according to the formula V = ab. 2 / 2 Calculate tumor volume, observe continuously for 21 days, results as follows Figure 5 As shown.
[0040] The results are as follows Figure 4 The figure shown is a graph illustrating the effect of a pancreatic cancer-specific binding peptide on the body weight of tumor-bearing mice. (Source: [Insert graph here]) Figure 4 It can be seen that during the entire 21-day observation period, the body weight of mice in both the experimental and control groups remained stable, with no significant decrease caused by the radiopharmaceutical, and there was no statistically significant difference in body weight change curves between the two groups. This indicates... 177Lu-DOTA--HFL2c exhibited good safety at the tested dose and did not produce significant systemic toxicity.
[0041] The results are as follows Figure 5 The figure shown is a graph illustrating the effect of a pancreatic cancer-specific binding peptide on the volume of subcutaneous xenografts in tumor-bearing mice. Figure 5 It was found that after injection of the pancreatic cancer-specific binding peptide, the growth of pancreatic cancer tumors with high CLDN18.2 expression was significantly inhibited, with slow tumor volume growth during the 21-day observation period, showing no statistically significant difference compared to pre-treatment levels. In contrast, the tumor volume of the control group with low CLDN18.2 expression continued to increase rapidly, and by day 14 after administration, its tumor volume was significantly higher than that of the experimental group before treatment and at the same time point.
[0042] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them. The basic principles and main features of the present invention have been described above with specific implementation schemes. Based on the present invention, some modifications or substitutions can be made, but these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of protection claimed by the present invention.
Claims
1. A pancreatic cancer-specific binding peptide, characterized in that, The pancreatic cancer-specific binding peptide is a chelating agent-mediated radionuclide-labeled HFL2c peptide; the radionuclide includes imaging radionuclides or therapeutic radionuclides; the amino acid sequence of the HFL2c peptide is shown in SEQ ID NO.
1.
2. The pancreatic cancer-specific binding peptide according to claim 1, characterized in that, The chelating agent is DOTA.
3. The pancreatic cancer-specific binding peptide according to claim 1, characterized in that, The imaging radionuclide is 68 Ga; the therapeutic radionuclide is 177 Lu.
4. The method for preparing a pancreatic cancer-specific binding peptide according to any one of claims 1-3, characterized in that, The preparation method specifically includes the following steps: (1) Dissolve the HFL2c peptide coupled with the chelating agent in sodium acetate buffer to obtain a mixed solution, and then add 68 Mix the GaCl3 solution and adjust the pH to 3.5-4.5; heat at 90-95℃ for 8-12 minutes to obtain the reaction solution; (2) The reaction solution obtained in step (1) was purified by C18 solid phase extraction column, washed with water, and then eluted with 50-70% (v / v) ethanol aqueous solution to obtain HFL2c peptide labeled with chelating agent-mediated imaging radionuclides.
5. A method for preparing a pancreatic cancer-specific binding peptide according to any one of claims 1-3, characterized in that, The preparation method specifically includes the following steps: (1) The HFL2c peptide coupled with the chelating agent and the free radical scavenger were mixed in ammonium acetate buffer to obtain a mixed solution, and then added 177 Mix with LuCl3 solution, adjust pH to 4.8-5.5; heat at 85-95℃ for 20-30 min to obtain reaction solution; (2) The reaction solution obtained in step (1) is purified by C18 solid phase extraction column, washed with water, and then eluted with 40-60% (v / v) ethanol aqueous solution to obtain chelating agent-mediated therapeutic radionuclide-labeled HFL2c peptide.
6. The method for preparing a pancreatic cancer-specific binding peptide according to claim 4, characterized in that, The concentration of the sodium acetate buffer solution is 0.2-0.3 M; the concentration of the HFL2c peptide conjugated with the chelating agent in the mixed solution is 18-22 μg / mL; the mixed solution and 68 The volume ratio of the GaCl3 solution is 1:
1.
7. The method for preparing a pancreatic cancer-specific binding peptide according to claim 5, characterized in that, The concentration of the ammonium acetate buffer is 0.1-0.2 M; the concentration of the HFL2c peptide coupled with the chelating agent in the mixed solution is 18-22 μg / mL; the free radical scavenger is gentianic acid, and its concentration in the ammonium acetate buffer is 10 mg / mL; the mixed solution and 177 The volume ratio of the LuCl3 solution is 2:
1.
8. The use of a pancreatic cancer-specific binding peptide according to any one of claims 1-3 in the preparation of a targeted drug for the treatment or diagnosis of pancreatic cancer.