Polypeptides targeting cd38 and uses thereof

Abstract

The present application relates to the biomedical technology field, especially to a kind of polypeptide targeting CD38 and its application.The present application provides polypeptide targeting CD38, the polypeptide specificity is high, sensitivity is good, molecular weight is small, biological safety is high, immunogenicity is low, tumor penetration is high.The polypeptide can be synthesized by chemical synthesis method, simple operation, low production cost.The small molecule polypeptide of the present application is more easily designed and modified, and can be further optimized as a multifunctional targeting material, which has strong practicability and application prospect.The polypeptide of the present application and the imaging agent are combined to prepare a molecular probe, which can overcome the defects of large molecular weight, easy inactivation, slow tissue penetration, slow blood clearance and the like of monoclonal antibody molecular probe.The polypeptide and its derivative products of the present application have excellent application prospect in tumor treatment, diagnosis and imaging.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to a polypeptide targeting CD38 and its applications. Background Technology

[0002] Multiple myeloma (MM) is an age-related malignant disease characterized by abnormal proliferation of bone marrow plasma cells and excessive production of monoclonal immunoglobulins or light chains (M protein). MM primarily affects the elderly, with an insidious onset, and most patients are diagnosed at an advanced stage. With an aging population, the incidence of MM is on the rise and has now surpassed that of acute leukemia. Its clinical manifestations are bone destruction, lacking specificity; diagnosis mainly relies on clonal plasma cell proliferation in bone marrow biopsy, an invasive procedure, and improper selection of the bone marrow biopsy site can lead to false negatives. CD38 is a multifunctional transmembrane glycoprotein with both enzymatic and receptor functions. CD38 is significantly overexpressed on the surface of malignant plasma cells in MM, making it a characteristic tumor biomarker of MM. Furthermore, CD38 plays an important role in tumor microenvironment interactions, regulation of immunosuppressive activity, and immune activation in lymphoma and other malignant tumors.

[0003] Daratumumab, a humanized immunoglobulin G1-kappa (IgG1-κ) antibody targeting the CD38 epitope, can specifically bind to the CD38 antigen on the cell surface and induce tumor cell death. It has shown good efficacy and safety in relapsed and refractory multifocal tumors (MM), but some patients with initially good response may experience attenuated reactivity or even drug resistance. Furthermore, a major limitation of imaging / diagnostic reagents based on intact antibodies is their long circulating half-life. In addition, the antibody preparation process is complex and costly, leading to expensive treatment. Moreover, as biological macromolecules, antibodies have poor penetration into solid tumors, strong immunogenicity, and many unavoidable side effects in clinical practice. Summary of the Invention

[0004] This invention analyzes the crystal structure of the CD38 and daratumumab complex, extracts the binding hotspot amino acid sites, performs single-point mutagenesis, and designs a peptide library using computer simulation. Candidate peptides are initially screened using docking scoring and binding energy. Subsequently, a series of high-affinity CD38 peptides are screened using surface plasmon resonance (SPRi) technology.

[0005] After screening, the CD38-targeting peptide of this invention was finally obtained. The CD38-targeting peptide provided by this invention has high specificity, good sensitivity, small molecular weight, high biosafety, low immunogenicity, high tumor penetration, and selectively binds to tumor cells with high CD38 expression. Based on this, the following invention is proposed.

[0006] In a first aspect, the present invention provides a polypeptide targeting CD38, the amino acid sequence of which is shown in SEQ ID No. 1.

[0007] In a second aspect, the present invention provides isomers, derivatives, pharmaceutically acceptable salts, hydrates or solvates of the above-mentioned polypeptides;

[0008] The derivative is a divalent or multivalent form of the polypeptide.

[0009] In this invention, the amino acid residues can be L-type, D-type, or a mixture of L-type and D-type.

[0010] In this invention, the isomers include sequence variants with reversed amino acid sequences or cyclic peptide structures.

[0011] In this invention, the divalent or multivalent can target CD38.

[0012] Preferably, the divalent or multivalent is formed by linking molecules via covalent or non-covalent linkage, or by mixing with polymers via non-covalent linkage.

[0013] Preferably, the covalently linked linker is at least one of fluorescein isothiocyanate, 6-tert-butoxycarbonylhydrazinoic acid, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide, N-hydroxysuccinimide, and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid.

[0014] Preferably, the non-covalently linked linker molecules include, but are not limited to, lipophilic near-infrared dyes.

[0015] Preferably, the polymer is at least one of polyethylene glycol (PEG), polyvinyl alcohol (PVA), cyclodextrin, polyamide-amine dendritic polymer (PAMAM), polylactic acid (PLA), and polylactic acid-ethanolamine (PLGA).

[0016] Thirdly, the present invention provides a nucleic acid encoding the polypeptide.

[0017] Fourthly, the present invention provides a biomaterial comprising the polypeptide, isomers of the polypeptide, derivatives, pharmaceutically acceptable salts, hydrates or solvates, or the nucleic acid; preferably, the biomaterial is a carrier, expression cassette, transposon, host cell or transgenic cell line.

[0018] In this invention, the vector includes, but is not limited to, cloning vectors, expression vectors, and plasmid vectors. All vectors containing at least one copy of the nucleic acid encoding the CD38-targeting polypeptide of this invention are within the scope of protection of this invention. The host cell or transgenic cell line can be a cell or cell line derived from microorganisms, plants, or animals. All host cells or transgenic cell lines containing at least one copy of the nucleic acid encoding the CD38-targeting polypeptide of this invention or containing a vector carrying at least one copy of the nucleic acid are within the scope of protection of this invention.

[0019] Preferably, the CD38-targeting peptide of the present invention is prepared by the Fmoc solid-phase peptide synthesis method.

[0020] Fifthly, the present invention provides a medicament comprising the polypeptide, isomers of the polypeptide, derivatives, pharmaceutically acceptable salts, hydrates or solvates, or the nucleic acid, or the biological material, and pharmaceutically acceptable excipients.

[0021] In some implementations, the drug also includes agents that kill tumor cells.

[0022] Preferably, the agent that kills tumor cells is at least one of the following: chemical drugs, biological drugs, nanomedicines, radiopharmaceuticals, photothermal therapy or photodynamic therapy drugs that kill tumor cells;

[0023] It may be at least one of alkylating agents, antimetabolites, antitumor natural drugs, antitumor antibiotics, hormones, metal complexes, or tumor radiotargeting markers.

[0024] In some implementations, the drug also includes a drug carrier.

[0025] The carrier includes, but is not limited to, carriers used for preparing targeted drugs.

[0026] Preferably, the carrier is at least one of nanomaterials, liposomes, or oily compounds.

[0027] Pharmaceutically acceptable excipients include adjuvants.

[0028] The drugs described above in this invention can be used for targeted therapy and combination therapy of various tumors.

[0029] In a sixth aspect, the present invention provides a conjugate comprising a carrier and at least one selected from the following components: the polypeptide, or the isomer, derivative, pharmaceutically acceptable salt, hydrate or solvate, or the nucleic acid, or the biological material.

[0030] In the coupling, the carrier is obtained by covalently or non-covalently connecting or interacting with the above-mentioned components.

[0031] Preferably, the carrier is any one or more of fluorescein, antibody, polymer, high molecular weight material, nanomaterial, liposome, oily compound, and inorganic material.

[0032] More preferably, the polymeric material is at least one of polyester, polyanhydride, polyamide phospholipid polymer micelles, polylactic acid-glycolic acid copolymer, polyethylene glycol, and chitosan.

[0033] More preferably, the inorganic material is at least one of nano-gold, carbon materials, calcium materials, magnetic materials, mesoporous silicon materials, and quantum dots.

[0034] In a seventh aspect, the present invention provides an imaging formulation comprising an imaging agent and at least one selected from the following components: the polypeptide, or the isomer, derivative, pharmaceutically acceptable salt, hydrate or solvate, or the nucleic acid, or the biomaterial, or the drug, or the conjugate;

[0035] The imaging agent is at least one of a radionuclide, a radionuclide label, a fluorescent molecule, a magnetic resonance contrast agent, or a molecular imaging preparation.

[0036] In the imaging formulation, the imaging agent and the components are present in a coupled or mixed form.

[0037] The imaging formulation of this invention can monitor the efficacy of immunotherapy in real time and can be used as a predictive and companion diagnostic reagent for CD38 immunotherapy.

[0038] Eighthly, the present invention provides a reagent or kit comprising the said polypeptide, or the said isomer, derivative, pharmaceutically acceptable salt, hydrate or solvate, or the said nucleic acid, or the said biomaterial, or the said drug, or the said conjugate, or the said imaging preparation.

[0039] In a ninth aspect, the present invention provides the use of the said polypeptide, or the said isomer, derivative, pharmaceutically acceptable salt, hydrate or solvate, or the said nucleic acid, or the said biomaterial, or the said drug, or the said conjugate, or the said imaging preparation, or the said reagent or kit in at least one of the following aspects:

[0040] (1) Detect the expression level of CD38 in cells;

[0041] (2) Preparation of reagents for detecting CD38 expression levels in cells;

[0042] (3) Preparation of pharmaceutical products; said pharmaceutical products are used for the diagnosis, prevention or treatment of diseases with abnormal CD38 expression;

[0043] (4) Drug carrier.

[0044] Preferably, the disease with abnormal CD38 expression is at least one of tumors, rheumatoid arthritis, atherosclerosis, and coronary heart disease.

[0045] More preferably, the tumor is at least one of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL).

[0046] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0047] The peptides of this invention exhibit high specificity and sensitivity, small molecular weight, high biocompatibility, low immunogenicity, and high tumor penetration. These peptides can be synthesized using chemical synthesis methods, which are simple to operate and have low production costs. The small molecule peptides of this invention are easier to design and modify for drug development, and can be further optimized into multifunctional targeting materials, demonstrating strong practicality and application prospects. Combining the peptides of this invention with imaging agents to prepare molecular probes can overcome the shortcomings of monoclonal antibody molecular probes, such as large molecular weight, easy inactivation, slow tissue penetration, and slow blood clearance. The peptides of this invention and their derivatives have excellent application prospects in tumor treatment, diagnosis, and imaging. Attached Figure Description

[0048] Figure 1 This is a mass spectrometry identification diagram of the CP1 polypeptide after solid-phase synthesis according to the present invention.

[0049] Figure 2 This is a surface plasmon resonance result of the affinity between the CP1 polypeptide and human CD38 protein provided by this invention.

[0050] Figure 3 This is a graph showing the specific affinity test results of the FITC-labeled peptide provided by this invention with the CD38-positive cell line Ramos and the CD38-negative cell line U266.

[0051] Figure 4 It is a small animal in vivo fluorescence imaging using peptide probes.

[0052] Figure 5 yes 68 The labeling rate of Ga-labeled CD38-targeting peptides and the results of radiochemically pure HPLC determination are shown in the figure.

[0053] Figure 6It is a small animal PET imaging display 68 The image shows the in vivo specificity of Ga-labeled CD38-targeting peptides in CD38-positive tumor Ramos and CD38-negative tumor U266.

[0054] Figure 7 yes 68 The image shows the SUV comparison results of Ga-labeled CD38-targeting peptides in CD38-positive tumor Ramos and CD38-negative tumor U266.

[0055] Figure 8 This is a statistical graph showing the differences in radioactive uptake distribution in various organs of mice with CD38-positive tumor Ramos and CD38-negative tumor U266. Detailed Implementation

[0056] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of this invention, not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0057] Unless otherwise specified, all methods used in the examples were conventional or performed according to techniques or conditions described in the literature in this field, or in accordance with the product instructions. Reagents and instruments used without specified manufacturers were all conventional products that could be purchased from legitimate channels.

[0058] Example 1: Preparation method of CD38-targeting peptide

[0059] After screening from a microchip-based combinatorial chemistry peptide library, the peptide was synthesized using a standard Fmoc protocol via solid-phase synthesis. The C-terminal carboxyl group of the target peptide was covalently linked to a polymer resin. Then, starting from the amino group of this amino acid, a peptide bond was formed by reacting with the carboxyl group of another amino acid. The solid-phase synthesis sequence proceeded from the C-terminus to the N-terminus, repeating the previous step to couple individual amino acids to the solid-phase resin until the target peptide product was obtained. After the reaction was complete, the protecting group was removed, and the peptide chain was separated from the resin using a lysis buffer to obtain the target product. MALDI-TOF identification and HPLC purification were used for subsequent experiments. The preferred peptide CP1 (SEQ ID No. 1) of this invention was obtained through chemical synthesis, and the mass spectrometry identification results are as follows: Figure 1 As shown, this confirms the correctness of the targeting peptide.

[0060] Example 2: Affinity of CP1 peptide with human CD38 protein

[0061] This embodiment uses the surface plasmon resonance (SPRi) method to detect the affinity between CP1 peptide and human CD38 protein. Specifically:

[0062] Spot the CP1 peptide solution onto the SPRi chip and incubate overnight at 4°C under humid conditions. Wash with 10×PBS for 10 min, then with 1×PBS for 10 min, and wash twice with deionized water for 10 min each time. Block with 5% skim milk overnight. Repeat the above washing steps, then dry with nitrogen and wait for instrumentation (Plexera). HT surface plasmon resonance imaging system.

[0063] The mobile phase was sequentially passed through CD38 protein samples at concentrations of 1×PBS, 2×PBS, 16.5 nM, 33 nM, 66 nM, 132 nM, and 264 nM, and the SPRi signal was recorded and analyzed.

[0064] Depend on Figure 2 It can be seen that the SPRi signal of CP1 gradually increases with increasing protein concentration, and the KD value reaches 10. -8 M indicates that the polypeptide of the present invention has a strong affinity for CD38, which can meet the requirements for subsequent in vivo application.

[0065] Example 3: Preparation of FITC-labeled peptides

[0066] The fluorescein isothiocyanate (FITC) conjugate was obtained by solid-phase synthesis, followed by conjugation of ε-aminohexanoic acid onto the solid-phase synthesized peptide resin. FITC was mixed with peptide beads and reacted overnight in a solution of pyridine / N,N-dimethylformamide / dichloromethane at a ratio of 1:5:7, protected from light. The FITC conjugate was obtained after lysis using a lysis buffer, identified by MALDI-TOF, and purified by HPLC for subsequent experiments.

[0067] Example 4: Cellular-level verification of the affinity of the CD38-targeting peptide

[0068] The positive cells selected for the experiment were Ramos, and the negative cells were U266. They were cultured in RPMI 1640 medium containing 10% FBS.

[0069] The target peptide interacted with positive and negative cells, respectively, and the binding was investigated using confocal microscopy. The specific experimental steps were as follows: Both types of cells were seeded onto confocal microplates and cultured overnight at 37°C in a 5% CO2 cell culture incubator. After cell adhesion, the culture medium was discarded, and the nuclei were stained with Hoechst 33342 reagent. The cells were incubated at room temperature for 10 min and washed twice with PBS. Then, 0.1 mg / mL of the peptide FITC conjugate was added, and the cells were incubated at 4°C in the dark for 20 min, followed by washing three times with PBS. The fluorescence distribution in the cells was detected using a laser scanning confocal microscope (ZEISS LSM 710).

[0070] The results are as follows Figure 3 As shown, Ramos cell membranes exhibit a clear green fluorescence signal from FITC, while U266 cell membranes show almost no fluorescence. The results indicate that the target peptides can effectively bind to the cell membranes of tumor cells with high CD38 expression, but cannot bind to those with low expression. This demonstrates that the CP1 peptide has specificity for CD38 recognition, consistent with the molecular-level SPRi data.

[0071] Example 5: In vivo high-sensitivity fluorescence imaging of peptide probes

[0072] Ramos cells were cultured in RPMI 1640 medium containing 10% fetal bovine serum at a concentration of 1×10⁻⁶. 6 The tumor was injected subcutaneously into the right hind limb of a Balb / c mouse until it reached 50 mm. 3 1 mg of ICG-CP1 peptide was weighed and dissolved in 1 mL of 1×PBS. 150 μL of the ICG-CP1 peptide probe was injected into the tail vein. Half an hour later, the signal was acquired using the IVIS Spectrum small animal in vivo optical three-dimensional imaging system. After 24 hours, the main organs were dissected and in vitro fluorescence distribution imaging was performed.

[0073] The results are as follows Figure 4 As shown, the peptide imaging agent prepared above was injected into CD38-positive tumor-bearing mice via the tail vein. Within 0.5 hours, the fluorescence signal at the tumor site gradually increased, reaching its peak at 2 hours, and then gradually decreased until 8 hours. Compared with the control dye alone, the tumor also showed a strong fluorescence signal after dissection, and there was also strong enrichment in the liver and kidneys. The above results demonstrate that the peptide small molecule probe of the present invention has rapid CD38 targeting and rapid clearance and metabolism, enabling high-sensitivity in vivo imaging of small tumors.

[0074] Example 6 ImmunoPET imaging of peptide probes in a tumor-bearing mouse model

[0075] All animal experiments in this embodiment were conducted in accordance with the protocols approved by the Animal Management and Use Committee of Peking University First Hospital.

[0076] CB17-SCID immunodeficient mice (4-6 weeks old, male) with dual T-cell and B-cell deficiencies were selected for constructing a subcutaneous lymphoma tumor model. Mice were randomly divided into two groups: an experimental group and a control group, with five mice in each group. CB17-SCID immunodeficient mice were a product of Beijing Vital River Laboratory Animal Technology Co., Ltd. Each mouse was subcutaneously injected with 1×10⁻⁶ T cells into the right axilla. 7 200 μL Matrigel suspension (Invitrogen, USA) of Ramos and U266 lymphoma cells. Mice were monitored for health and tumor volume every other day. Tumors reaching 1 cm in diameter could be used for in vivo imaging and biodistribution experiments.

[0077] Rinse with 0.6M high-purity hydrochloric acid 68 Ge- 68 GaCl3 solution was obtained using a Ga germanium-gallium generator. 1 mL of Ga-68 solution was taken, and 100 μL of sodium hydroxide (3M) and 130 μL of sodium acetate (3M) were added. The mixture was capped and mixed thoroughly. The pH was measured to be 4-4.5 using 0-6 precision pH paper. The molecule to be labeled was added to the prepared solution. Eluting was performed after heating at 90°C for ten minutes. After cooling the reaction solution, it was added to an activated Sep-Pak LightC18 column (5 mL ethanol, 5 mL deionized water, activated according to ethanol-water-air method). Impurities were rinsed with 3.0 mL of pure water and discarded. A 0.22 μm sterile microporous membrane was added, and the product was collected into a sterile vacuum bottle with 0.5 mL of ethanol solution. 5.0 mL of physiological saline was added to the system for later use.

[0078] 68 The Ga-DOTA-CD38 peptide-labeled product was further determined by high-performance liquid chromatography (HPLC). Chromatographic conditions: C18 column (4.6 × 150 mm, 5 μm, XBridge, Waters); mobile phase A: deionized water (0.1% trifluoroacetic acid); mobile phase B: acetonitrile (0.1% trifluoroacetic acid); flow rate: 1.0 mL / min. Specific analytical methods were: 0–2 min, 10% B; 2–10 min, 10%–60% B; 10–12 min, 60% B; 12–15 min, 60%–10% B. Radiometric spectra were collected.

[0079] The results are as follows Figure 5 As shown, the difference in retention times of the radiochromatographic peaks in the formulation is no greater than 0.5 min. 68 The Ga-DOTA-CD38 peptide-labeled product has a radiochemical purity of approximately 99.9%.

[0080] When the tumor diameter of the tumor-bearing mice reached approximately 1 cm, 5-10 MBq were injected via the tail vein.68 Ga-DOTA-CD38 peptide probe. PET imaging was performed using an Inveon micro-PET / CT scanner (Siemens, Germany) at 30, 40, 50, 60, 70, and 80 minutes post-injection. Regions of interest (ROIs) were plotted using Inveon software and quantitative analysis was performed to obtain the radioactivity concentration in tumors, cardiac blood pools (blood), liver, and kidneys at different time points in vivo. The content of the radioactive probe was expressed as the percentage of radioactivity count per gram of tissue relative to the total injected radioactivity count (%ID / g), representing the radioactive uptake.

[0081] The results are as follows Figure 6 As shown, maximum intensity projection (MIP) PET imaging results indicate that in a CD38-positive Ramos tumor model, in 68 Thirty minutes after injection of Ga-DOTA-CD38 peptide, significant radioactive accumulation was observed in the tumor, with high uptake remaining from 30 to 80 minutes. However, in the CD38-negative U266 tumor model, injection... 68 No significant radioactive accumulation was observed in the tumor at any time point after the Ga-DOTA-CD38 peptide probe was applied.

[0082] By using the corresponding software to draw the region of interest (ROI) and perform quantitative analysis, the radioactivity concentration of tumors at different time points in vivo was obtained.

[0083] The results are as follows Figure 7 As shown, Ramos tumors maintained high radioactive uptake for 30 to 80 minutes, and were higher than those in the negative control group.

[0084] During injection 68 After the Ga-DOTA-CD38 peptide probe was used, tumors, blood, heart, liver, spleen, lungs, kidneys, stomach, pancreas, small intestine, bladder, muscles, long bones of the lower leg, brain, and tail were dissected. The samples were weighed, and the radioactivity of the samples was counted using an automated gamma counter (PerkinElmer). The uptake of the radiotracer in different organs / tissues was calculated, and the biodistribution was calculated and expressed as %ID / g (mean ± SD).

[0085] Biological distribution results as follows Figure 8 As shown, Ramos tumor uptake (0.75 ± 0.03% ID g) -1 The value was higher than that of U266 tumors (0.26 ± 0.08% ID g). -1(p<0.01). Furthermore, the uptake of the radiotracer in the lungs of Ramos tumor-bearing mice was 8.92% ID g. -1 The liver uptake was 4.03 ± 0.09% ID g. -1 The renal uptake was 18.38 ± 0.82% ID g. -1 All were higher than the uptake in various organs of U266 tumor-bearing mice (3.67 ± 0.51% ID g, respectively). -1 1.47±0.25% ID g -1 12.41±3.39% ID g -1 The results are consistent with those of PET imaging.

[0086] The above results demonstrate that the polypeptide small molecule probe of the present invention has rapid CD38 targeting ability and good tumor penetration ability, which can realize high-sensitivity in vivo imaging of small tumors.

[0087] In summary, the polypeptide of the present invention has the characteristic of targeting CD38-positive tumor cells. Therefore, in practical applications, the polypeptide of the present invention can be used as a homing peptide and combined with anticancer drugs or imaging agents for targeted tumor therapy and imaging.

[0088] 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; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A polypeptide targeting CD38, characterized in that, Its amino acid sequence is shown in SEQ ID No.

1.

2. A pharmaceutically acceptable salt or solvate of the polypeptide of claim 1.

3. The hydrate of the polypeptide of claim 1.

4. A nucleic acid encoding the polypeptide of claim 1.

5. A biomaterial, characterized in that, It expresses the polypeptide of claim 1 or contains the nucleic acid of claim 4; the biological material is a vector, expression cassette, transposon, host cell or transgenic cell line.

6. A drug, characterized in that, It includes the polypeptide of claim 1, or a pharmaceutically acceptable salt or solvation of the polypeptide of claim 2, or a hydrate of the polypeptide of claim 3, or a nucleic acid of claim 4, or a biomaterial of claim 5, and pharmaceutically acceptable excipients.

7. An imaging formulation, characterized in that, It includes an imaging agent and at least one of the following components: the polypeptide of claim 1, or a pharmaceutically acceptable salt or solvate of the polypeptide of claim 2, or a hydrate of the polypeptide of claim 3, or a nucleic acid of claim 4, or a biomaterial of claim 5, or a drug of claim 6; The imaging agent is at least one of a radionuclide, a magnetic resonance imaging agent, or a molecular imaging preparation.

8. The imaging formulation according to claim 7, characterized in that, The molecular imaging agent is a radionuclide marker or a fluorescent molecule.

9. A reagent or kit, characterized in that, It includes the polypeptide of claim 1, or a pharmaceutically acceptable salt or solvation of the polypeptide of claim 2, or a hydrate of the polypeptide of claim 3, or a nucleic acid of claim 4, or a biological material of claim 5, or a drug of claim 6, or an imaging preparation of claim 7 or 8.

10. The use of the polypeptide of claim 1, or a pharmaceutically acceptable salt or solvation of the polypeptide of claim 2, or a hydrate of the polypeptide of claim 3, or a nucleic acid of claim 4, or a biomaterial of claim 5, or a drug of claim 6, or an imaging formulation of claim 7 or 8, or a reagent or kit of claim 9, in at least one of the following aspects: (1) Preparation of reagents for detecting CD38 expression levels in cells; (2) Preparation of drug carrier.

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