D-cyclic peptide dimers, pet imaging agents thereof, and methods of making and using the same

Abstract

The application belongs to the technical field of biomedicine, and provides a D-type ring peptide dimer targeting plectin. The D-type ring peptide dimer comprises two D-type ring peptide monomers, each of which is composed of D-type amino acids and has a cyclic structure, and the D-type ring peptide monomers have a binding capacity targeting plectin, and the amino acid sequence is D-type KTLLPTP. The application also relates to a radionuclide label as a positron emission tomography (PET) imaging agent, a preparation method thereof and application thereof in tumor PET imaging. Through the synergistic effect of D-type amino acid replacement, cyclization structure modification and dimerization design, the targeting capacity of the polypeptide is significantly improved, excellent PET imaging effects are shown in a plectin high-expression tumor model, the tumor / background ratio is high, imaging is clear, and the polypeptide has good clinical transformation potential.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, specifically relating to D-type cyclic peptide dimers targeting plectin and their radionuclide labels as positron emission tomography (PET) imaging agents, as well as their preparation methods and applications in tumor PET imaging. Background Technology

[0002] PET, with its advantages of high sensitivity, high spatial resolution, and quantitative analysis capabilities, has become an important tool for early diagnosis, staging, and efficacy evaluation of tumors. The key to PET imaging lies in the development of high-performance molecular probes. Molecular probes generally consist of two parts: a targeting ligand and a positron-emitting nuclide. They utilize ligand-receptor specific binding to achieve active targeted molecular imaging.

[0003] Plectin is a skeletal protein with a molecular weight of approximately 500 kDa that is highly expressed in various malignant tumors, including pancreatic cancer, glioma, hepatocellular carcinoma, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, and non-small cell lung cancer. It promotes tumor growth, proliferation, and migration. Therefore, plectin is a potential target for developing molecular imaging probes for tumors.

[0004] Plectin-targeted peptide (PTP) is a heptapeptide screened from a phage display peptide library. Its amino acid sequence is Lys-Thr-Leu-Leu-Pro-Thr-Pro (KTLLPTP), and it specifically binds to plectin. Compared to antibodies, PTP peptides have advantages such as small molecular weight, low immunogenicity, and ease of chemical modification.

[0005] However, existing PTP peptide-based imaging probes have the following technical problems: First, it has poor stability in vivo. Natural L-type polypeptides are easily hydrolyzed by proteases in the body, resulting in a short biological half-life, insufficient uptake and retention at the tumor site, and affecting imaging results.

[0006] Second, the target affinity is limited. The binding affinity between monomeric peptides and targets is usually limited, making it difficult to obtain an ideal tumor / background ratio for tumors with low target expression levels.

[0007] Third, existing radiolabeled PTP probes are mainly concentrated in the field of SPECT imaging (such as...). 99m Tc labeling), while SPECT is inferior to PET in terms of sensitivity and spatial resolution, and there are no reports of PET probes based on D-cyclic peptide dimers.

[0008] US Patent US2011182814A1 and Chinese Patent CN102762984A disclose tetrameric complexes of L-type linear PTP monomers for detection and imaging. However, these probes still have an L-type linear structure, which is not stable enough in vivo. They also use fluorescence or SPECT imaging methods and do not involve PET imaging. Summary of the Invention

[0009] The first technical problem to be solved by the present invention is to provide a plectin-targeted D-cyclic peptide dimer.

[0010] The second technical problem to be solved by the present invention is to provide a PET imaging agent for the D-type cyclic peptide dimer, namely a radionuclide-labeled D-type cyclic peptide dimer.

[0011] The third technical problem to be solved by the present invention is to provide a method for preparing the PET developer.

[0012] The fourth technical problem to be solved by the present invention is to provide the application of the PET imaging agent in tumor PET imaging.

[0013] To address the aforementioned problems, this invention proposes a comprehensive solution: by replacing all amino acids of the PTP peptide with D-isomers, designing a cyclic structure, and constructing it as a dimer, a further development is undertaken. 68 Ga and 18 F-labeled PET imaging agents. The D-type polypeptide resists protease hydrolysis, the cyclized structure further constrains the conformation and enhances stability, and the dimerization strategy enhances target affinity through multivalent effects. The synergistic effect of these three factors makes the PET imaging agent of this invention significantly superior to existing technologies in terms of in vivo stability, targeting, and imaging performance. This invention is based on the above research.

[0014] In a first aspect, the present invention provides a D-cyclic peptide dimer. The D-cyclic peptide dimer comprises two D-cyclic peptide monomers, each of which is composed of a cyclic polypeptide consisting of D-amino acids, and the D-cyclic peptide monomers have the ability to bind to reticulin targets.

[0015] Preferably, the amino acid sequence of the D-type cyclic peptide monomer is D-type KTLLPTP (SEQ ID NO 1, D PTP), that is D Lys- D Thr- D Leu- D Leu- D Pro- D Thr- D Pro.

[0016] Preferably, the cyclic structure is achieved by cyclization of the first and last amide bonds or by forming a disulfide bond between two D-cysteine ​​residues.

[0017] Preferably, the two D-type cyclic peptide monomers are covalently linked by a linker arm selected from aspartic acid or glutamic acid.

[0018] Secondly, the present invention provides a PET developer.

[0019] Imaging agents primarily refer to radiopharmaceuticals introduced into the body in nuclear medicine that can perform imaging of organs, tissues, or molecules. In some radiological examinations, the term also broadly refers to contrast agents. PET imaging agents, short for positron emission tomography (PET) tracers, are radiolabeled compounds used in PET (positron emission tomography) examinations. After injection into the body, they specifically accumulate in metabolically active lesions (such as tumors, epileptic foci, and areas of myocardial ischemia), thereby generating functional metabolic images by detecting the positron signals released. The PET imaging agent described in this invention contains the aforementioned D-cyclic peptide dimer. Preferably, the PET imaging agent also contains a bifunctional chelating agent and a positron-emitting radionuclide, with the structural formula: positron-emitting radionuclide-bifunctional chelating agent-D-cyclic peptide dimer.

[0020] Preferably, the bifunctional chelating agent is selected from NOTA, NODAGA, or DOTA.

[0021] Preferably, the bifunctional chelating agent is linked to a free carboxyl group of aspartic acid or glutamic acid.

[0022] Preferably, the positron-emitting radionuclide is selected from... 68 Ga or 18 F (with Al) 18 F-form notation).

[0023] Preferably, when the radionuclide is 68 When Ga is used, the bifunctional chelating agent is Nota, NODAGA, or DOTA, and the PET developer is [ 68 Ga]Ga-NOTA- D PTP2 dimer, [ 68 Ga]Ga-NODAGA- D PTP2 dimer or [ 68 Ga]Ga-DOTA- D PTP2 dimer.

[0024] Preferably, when the radionuclide is 18 At time F, with Al 18 F-type labeling, the bifunctional chelating agent is NOTA, and the PET developer is […]. 18 F]AlF-NOTA- DPTP2 dimer or Al[ 18 F]F-NOTA- D PTP2.

[0025] Thirdly, the present invention provides a method for preparing a PET developer. This preparation method includes the following steps: (a) Synthesizing D-type cyclic peptide dimers modified with chelating agents; (b) Label the product obtained in step (a) with a positron-emitting radionuclide to obtain a PET imaging agent.

[0026] Preferably, in step (b), when the positron-emitting radionuclide is 68 For Ga, the labeling reaction is carried out at room temperature and pH = 4.0-5.0 for 5-20 minutes; more preferably, at pH 4.5-5.0 for 10-15 minutes. Room temperature refers to indoor temperature, typically 18-26°C, preferably 22-24°C.

[0027] Preferably, in step (b), when the positron-emitting radionuclide is 18 When F, use Al 18 For the F labeling method, the reaction temperature is 90-100 ℃ for 5-20 minutes and the pH is 4.0-5.0, or the reaction temperature is 95-98 ℃ and the reaction time is 10-15 minutes.

[0028] Fourthly, the present invention provides the application of the PET imaging agent in the preparation of tumor PET images.

[0029] The D-type cyclic peptide dimer and its PET imaging agent of the present invention can be used as tumor PET imaging agents for early diagnosis, staging and efficacy evaluation of tumors with high plectin expression, and have broad clinical application prospects and commercial value.

[0030] The D-cyclic peptide dimer of the present invention can be used to prepare tumor PET imaging kits. The PET imaging kit contains the D-cyclic peptide dimer of the present invention or a D-cyclic peptide dimer modified with a bifunctional chelating agent. The PET imaging kit may contain related instructions, positive controls, negative controls, consumables, or solvents, etc.

[0031] Preferably, the imaging time in the tumor PET imaging kit is 0.5-2 hours. More preferably, it is 0.5-1 hour.

[0032] The term "radioactive concentration," in short, refers to the phenomenon where, in a scanned image, a particular area of ​​radioactive tracer (developer) accumulates in greater quantity and brightness than the surrounding normal tissue. Test results show that the PET imaging agent containing D-cyclic peptide dimers of this invention can effectively visualize the liver, spleen, heart, and soft tissues, and exhibits better radioactive concentration in the kidneys and bladder. Furthermore, the PET imaging agent containing D-cyclic peptide dimers has a significantly higher tumor / muscle ratio than the corresponding non-cyclic peptide dimer PET imaging agent.

[0033] The term "tumor uptake" refers to the ability of tumor cells to absorb extracellular substances. This process typically involves the entry, absorption, and distribution of substances; different tumor types and individual differences can affect the degree and rate of uptake. Tumor uptake has become an important branch of oncology research, providing significant guidance for tumor diagnosis and treatment. Tumor uptake is a crucial step in tumor therapy. Changes in the uptake capacity of tumor cells and intracellular signal transduction have a significant impact on the effectiveness and prognosis of tumor treatment. Test results show that, for most tissues, the tumor uptake of the D-cyclic peptide dimer-containing PET imaging agent of this invention is significantly higher than that of the corresponding non-cyclic peptide dimer PET imaging agent. Overall, the D-cyclic peptide dimer PET imaging agent of this invention is significantly superior to the L-linear monomer control in tumor imaging.

[0034] The terms “cell,” “cell line,” and “cell culture” are used interchangeably. All these terms include their offspring, which can be any and all progeny. It should be understood that all progeny may differ due to intentional or accidental mutations.

[0035] The term "cancer" refers to uncontrolled cell proliferation—leading to unregulated growth, lack of differentiation, local tissue invasion, and metastasis. Preferably, the tumor is a tumor that highly expresses the plectin protein, including but not limited to one or more of pancreatic cancer, glioma, hepatocellular carcinoma, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, or non-small cell lung cancer, etc.

[0036] In the description of this application, the terms "comprising," "including," or any other variations thereof are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising a reference structure" does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element.

[0037] It should be noted that in this article, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations.

[0038] As used herein, the term “about” typically means + / - 5% of the value, more typically + / - 4% of the value, more typically + / - 3% of the value, more typically + / - 2% of the value, more typically + / - 1% of the value, and even more typically + / - 0.5% of the value. As used herein, “1E5”, “1E7”, “1E8”, and “1E10” refer to 1x10^5, 1x10^7, 1x10^8, and 1x10^10, respectively.

[0039] Throughout this disclosure, certain embodiments may be disclosed in a range format. It should be understood that the range format is merely for convenience and brevity and should not be construed as a limitation on the scope of protection of the disclosed range. Therefore, the range description should be considered to specifically disclose all possible subranges and the individual values ​​within those ranges. For example, a description of a range such as 1 to 6 should be considered to have specifically disclosed subranges, such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., and the individual numbers within those ranges, such as 1, 2, 3, 4, 5, and 6. The range is not limited to integers and may include decimal measurements. This applies regardless of the width of the range.

[0040] As used herein, the term "amino acid" is intended to include both natural and synthetic amino acids, as well as D- and L-amino acids. "Standard amino acid" refers to any one of the twenty standard L-amino acids commonly found in naturally occurring peptides. "Non-standard amino acid residue" refers to any amino acid other than the standard amino acids, whether synthesized or derived from a natural source. As used herein, "synthetic amino acid" also includes chemically modified amino acids, including but not limited to salts, amino acid derivatives (e.g., amides), and substitutes. Amino acids contained in the peptides of the present invention can be modified by methylation, amidation, acetylation, or substitution with other chemical groups that alter the cyclic half-life of the peptide without adversely affecting its activity, particularly amino acids located at the carboxyl or amino terminus. Additionally, disulfide bonds may or may not be present in the peptides of the present invention.

[0041] Compared with the prior art, the present invention has the following outstanding advantages: (1) This invention is the first to comprehensively apply D-type amino acid substitution, cyclization structure modification, and dimerization design to PTP peptides, constructing D-type cyclic peptide dimers. The synergistic effect of the three structural modification strategies makes the peptide ligands of this invention significantly superior to existing L-type linear PTP monomers and their polymers in terms of in vivo stability and targeting affinity.

[0042] (2) The PET imaging agent of the present invention is composed of all D-type amino acids, which resists the hydrolytic degradation of proteases in the body and has a significantly prolonged half-life in plasma, providing a sufficient time window for tumor targeted uptake and PET imaging.

[0043] (3) The PET imaging agent of the present invention introduces a multivalent effect through dimerization design. The two targeting units can bind to the plectin target at the same time, which increases the binding affinity by more than an order of magnitude, thereby obtaining higher tumor uptake and clearer imaging effect.

[0044] (4) The present invention adopts 68 Ga and 18 F-labeled PET imaging probes targeting plectin were developed, filling a gap in the field of PET probes. Compared with existing SPECT imaging techniques, PET imaging offers higher sensitivity, better spatial resolution, and quantitative analysis capabilities.

[0045] (5) The PET imaging agent of the present invention is rapidly excreted in the kidneys and bladder, with low background in the liver and soft tissues, high tumor / background ratio, and excellent imaging effect. Attached Figure Description

[0046] To more clearly illustrate the technical solutions of this application, the drawings used in the embodiments will be briefly introduced below. Obviously, each drawing described below is for a part of the embodiments of this application. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0047] Figure 1 This is a schematic diagram of the structure of the D-type cyclic peptide dimer of the present invention, using NOTA- D Take PTP2 as an example.

[0048] Figure 2 yes[ 68 Ga]Ga-NOTA- D Radio-HPLC spectrum of PTP2.

[0049] Figure 3 It is Al[ 18 F]F-NOTA- D Radio-HPLC spectrum of PTP2.

[0050] Figure 4 yes[ 68 PET / CT image of Ga-NOTA-PTP in nude mice bearing pancreatic cancer.

[0051] Figure 5 yes[ 68 Ga]Ga-NOTA- D PET / CT image of PTP2 in nude mice bearing pancreatic cancer.

[0052] Figure 6 It is Al[ 18 F]F-NOTA- D PET / CT image of PTP2 in nude mice bearing pancreatic cancer.

[0053] Figure 7 yes[ 68 Ga]Ga-NOTA-PTP, [ 68 Ga]Ga-NOTA- D PTP2 and Al[ 18 F]F-NOTA- D Comparison of PTP2 uptake in tumor-bearing nude mice. Detailed Implementation

[0054] This invention discloses a D-cyclic peptide dimer, a PET imaging agent, its preparation method, and its applications. The D-cyclic peptide dimer comprises two D-cyclic peptide monomers, each composed of D-amino acids and having a cyclic structure, exhibiting binding ability to target reticulin. The PET imaging agent comprises the D-cyclic peptide dimer, a bifunctional chelating agent, and a positron-emitting radionuclide, wherein the positron-emitting radionuclide is selected from... 68 Ga or 18 F. This invention significantly enhances the targeting ability of peptides through the synergistic effect of D-type amino acid substitution, cyclization structure modification, and dimerization design. It demonstrates excellent PET imaging results in a plectin-overexpressing tumor model, with a high tumor / background ratio and clear imaging, showing good potential for clinical translation.

[0055] The technical solution will be clearly and completely described below through embodiments of this application. Obviously, the described embodiments are only some preferred embodiments of this application, and not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the protection scope of this application.

[0056] Example 1: [ 68 Ga]Ga-NOTA- D Preparation of PTP2 Take NOTA-D PTP2 was dissolved in 1.5 M sodium acetate to prepare a 1 mg / mL solution. From 68 Ge / 68 Ga generator rinses fresh 68 GaCl3 (1 mL, 185-370 MBq), take 100 μL NOTA- D PTP2 solution and rinsing 68 The GaCl3 solution was mixed and reacted at 95°C for 10 minutes. After the reaction, the radiochemical purity was determined by Radio-HPLC. The radiochemical purity was >95%. Figure 2 ).

[0057] Example 2: Al[ 18 F]F-NOTA- D PTP2 preparation Take NOTA- D PTP2 was dissolved in DMF to prepare a 1 mg / mL solution. 25 μL of AlCl3 solution (0.4 mM, prepared with 0.1 M sodium acetate buffer, pH = 4.0) was mixed with 20 μL of NOTA- D Mix the PTP2 dimer solution and add [ 18 [F] Fluoride ion solution (100 μL, approximately 185-370 MBq), reacted at 90 °C for 10 min. After the reaction, purified using a Sep-Pak C18 column, radiochemical purity determined by Radio-HPLC was >95%. Figure 3 ).

[0058] Example 3: PET / CT Imaging and Comparison Experiment of Glioblastoma-Bearing Nude Mice A subcutaneous nude mouse model of pancreatic cancer bearing BxPC-3 was established (n = 3), and [BxPC-3 was injected via tail vein]. 68 Ga-NOTA-PTP (200 μL, approximately 3.7 MBq) was injected into small animals, and PET / CT imaging was performed at 0.5, 1, and 2 hours post-injection. Results showed that... 68 Ga-NOTA-PTP showed significant radioactivity concentration at the pancreatic cancer tumor site, with a tumor / muscle ratio exceeding 5.5 after 0.5 hours. The radioactivity was primarily distributed in the kidneys and bladder, indicating that the imaging agent was mainly excreted through the urinary system. The liver, spleen, heart, and soft tissues showed weak contrast with a clear background. Figure 4 ).

[0059] Example 4: [ 68 Ga]Ga-NOTA- D PTP2 in PET / CT imaging of nude mice bearing pancreatic cancer Following the method of Example 3, using [ 68Ga]Ga-NOTA- D PET / CT imaging of nude mice bearing pancreatic cancer BxPC-3 with PTP2 (200 μL, approximately 7.4 MBq) showed that... 68 Ga]Ga-NOTA- D PTP2 shows significant radioactivity concentration at the pancreatic cancer tumor site, with a tumor / muscle ratio exceeding 7.5 after 0.5 hours. The radioactivity distribution in other organs is mainly similar to […]. 68 Ga]Ga-NOTA-PTP is similar ( Figure 5 ).

[0060] Example 5: Al[ 18 F]F-NOTA- D PTP2 in PET / CT imaging of tumor-bearing nude mice Following the method of Example 3, using Al[ 18 F]F-NOTA- D PET / CT imaging of nude mice bearing pancreatic cancer BxPC-3 with PTP2 (200 μL, approximately 7.4 MBq) showed that Al[ 18 F]F-NOTA- D PTP2 shows significant radioactivity concentration at the pancreatic cancer tumor site, with a tumor / muscle ratio exceeding 8.4 after 0.5 hours. The radioactivity distribution in other organs is mainly similar to […]. 68 Ga]Ga-NOTA-PTP is similar ( Figure 6 ).

[0061] Example 6: Comparison of biological distribution Thirty-six nude mice bearing pancreatic cancer BxPC-3 were randomly divided into three groups (n=4 per group) and injected via tail vein. 68 Ga]Ga-NOTA-PTP, [ 68 Ga]Ga-NOTA- D PTP2 and Al[ 18 F]F-NOTA- D PTP2 (dose of 200 μL, approximately 1.85 MBq). Animals were sacrificed at 0.5, 1, and 2 hours after injection, and tissues such as tumor, blood, heart, liver, spleen, lung, kidney, muscle, stomach, and small intestine were collected, weighed, and radioactivity counts were determined. The percentage of injected dose per gram of tissue (%ID / g) was calculated.

[0062] The results showed that: 0.5 hours, [ 68 Ga]Ga-NOTA- D The tumor uptake in the PTP2 group (%ID / g = 2.64 ± 0.11) was significantly higher than that in the [ 68Ga]Ga-NOTA-PTP group (%ID / g = 1.75 ± 0.13, p<0.01), Al[ 18 F]F-NOTA- D The PTP2 group had higher tumor uptake (%ID / g = 2.87 ± 0.10); the tumor / muscle ratio at 0.5 hours was 5.5 ([ 68 Ga]Ga-NOTA-PTP), 7.5 ([ 68 Ga]Ga-NOTA- D PTP2), 8.4 (Al[ 18 F]F-NOTA- D PTP2). Renal uptake is the highest, and the imaging agent is mainly excreted through the urinary system; uptake in non-target tissues such as the liver, spleen, lungs, and muscles is relatively low. Compared to [ 68 Ga]Ga-NOTA-PTP group, [ 68 Ga]Ga-NOTA- D PTP2 and Al[ 18 F]F-NOTA- D PTP2 has lower renal uptake ( Figure 7 The above results indicate that the D-type cyclic peptide dimer PET imaging agent of the present invention is significantly superior to the L-type linear monomer control in tumor imaging.

[0063] The embodiments described above are merely specific implementations of this application, but the scope of protection of this application is not limited thereto. Any variations or substitutions that can be conceived by those skilled in the art within the scope of the technology disclosed in this application without creative effort should be included within the scope of protection of this application. Therefore, the scope of protection of this application should be determined by the scope of protection of the claims in this application.

Claims

1. A D-type cyclic peptide dimer, characterized in that, The D-cyclic peptide dimer comprises two D-cyclic peptide monomers, each of which is composed of D-amino acids and has a cyclic structure. The D-cyclic peptide monomers have the ability to target plectin binding, and the amino acid sequence of the D-cyclic peptide monomers is D-KTLLPTP.

2. The D-type cyclic peptide dimer according to claim 1, characterized in that, The amino acid sequence of the D-type cyclic peptide monomer is as follows: D Lys- D Thr- D Leu- D Leu- D Pro- D Thr- D Pro.

3. The D-type cyclic peptide dimer according to claim 1, characterized in that, The cyclic structure is achieved through cyclization of the initial and final amide bonds or through the formation of a disulfide bond between two D-cysteine ​​residues; or... Two D-type cyclic peptide monomers are covalently linked by a linker arm selected from aspartic acid or glutamic acid.

4. A PET developer, characterized in that, The PET imaging agent comprises the D-type cyclic peptide dimer as described in any one of claims 1-3.

5. The PET developer according to claim 4, characterized in that, The PET imaging agent comprises a bifunctional chelating agent and a positron-emitting radionuclide, wherein the bifunctional chelating agent is selected from, but is not limited to, Nota, Nodaga, or Dota; and the positron-emitting radionuclide is selected from, but is not limited to, [other types of radionuclides]. 68 Ga or 18 F.

6. The PET developer according to claim 4, characterized in that, The PET developer is selected from, but not limited to, […]. 68 Ga]Ga-NOTA- D PTP2 or Al[ 18 F]F-NOTA- D PTP2.

7. The method for preparing the PET developer according to any one of claims 4-6, characterized in that, Includes the following steps: (a) Synthesizing the D-type cyclic peptide dimer according to any one of claims 1-3; (b) The D-cyclic peptide dimer was coupled with a bifunctional chelating agent to obtain a chelating agent-modified D-cyclic peptide dimer; (c) Label the product obtained in step (b) with a positron-emitting radionuclide to obtain a PET imaging agent.

8. The preparation method according to claim 1, characterized in that, In step (c), when the positron-emitting radionuclide is 68 When Ga is used, the labeling reaction is carried out at room temperature and pH 4.0-5.0 for 5-15 minutes; when the positron-emitting radionuclide is... 18 When F, use Al 18 F labeling method, react at 90-110℃ for 10-20 minutes.

9. The use of the PET imaging agent according to any one of claims 4-6 in the preparation of tumor PET imaging kits or imaging agents.

10. The application according to claim 1, characterized in that, The tumors mentioned are tumors that express plectin protein, including but not limited to pancreatic cancer, glioma, hepatocellular carcinoma, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, or non-small cell lung cancer.

11. A tumor PET imaging kit, characterized in that, The kit contains the D-cyclic peptide dimer as described in any one of claims 1-3, or The D-type cyclic peptide dimer of any one of claims 1-3 modified with a bifunctional chelating agent.

12. The tumor PET imaging kit according to claim 11, characterized in that, In the tumor PET imaging kit described above, the imaging time is 0.5-2 hours.

Images