Radioactive probes targeting angiotensin II based on the S protein sequence of SARS-CoV series viruses
By designing a radioactive probe [68Ga]Ga-A1/A3/A15 based on the S protein sequence of the SARS-CoV series viruses, the problems of slow in vivo clearance and unclear binding sites of existing probes were solved, achieving high affinity and high specificity for the ACE2 receptor, which is suitable for lung cancer PET imaging and the study of the mechanism of the novel coronavirus.
Patent Information
- Application Number
- CN202310608270.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-05-27
- Publication Date
- 2025-10-31
- Estimated Expiration
- 2043-05-27
AI Technical Summary
Existing radioactive probes are slow to clear in vivo, have unclear binding sites, and are widely expressed in normal human tissues, resulting in poor uptake and retention by tumor cells, making it difficult to meet the needs of research on the mechanism of the novel coronavirus and tumor diagnosis.
We designed radioactive probes targeting angiotensin II based on the S protein sequence of SARS-CoV series viruses, using Ga-68 labeled peptides such as [68Ga]Ga-A1/A3/A15, which, through high affinity binding to the ACE2 receptor, optimized the uptake and metabolic properties of tumor cells.
It achieves high affinity and high specificity for angiotensin receptor II, making it suitable for PET imaging of lung cancer and research on the mechanism of SARS-CoV-2, and has good in vivo bio-metabolic properties.
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Figure CN116570736B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to a radioactive probe targeting angiotensin II based on the S protein sequence of SARS-CoV series viruses, belonging to the field of radiopharmaceutical chemistry. Background Technology
[0002] Recent and early studies have shown that the binding of human angiotensin receptor II (ACE2) to the SARS-CoV-2 S protein plays a decisive role in viral invasion of cells. In March 2020, the full structure of the SARS-CoV-2 receptor ACE2, analyzed by cryo-electron microscopy, was published. The S1 subunit of the peptidase domain of the SARS-CoV-2 S protein is responsible for discovering and anchoring cells expressing the ACE2 receptor. After the receptor-binding domain (RBD) of the S1 subunit binds to the ACE2 receptor in human cells, the S2 subunit undergoes a conformational change to facilitate viral entry into the cell. The analysis of the full structure of ACE2 provides important structural biology support for the subsequent development of vaccines and antiviral drugs.
[0003] Because ACE2 is widely distributed in human tissues, SARS-CoV-2, in addition to invading the respiratory tract and lungs, also causes other symptoms and long-term sequelae in the digestive tract, cardiovascular system, and even the central nervous system. Furthermore, ACE2 is closely related to tumor formation, and is associated with the proliferation, angiogenesis, metabolism, metastasis, and invasion of tumors such as papillary / clear cell renal cell carcinoma, lung cancer, and gallbladder cancer. Various probes targeting ACE2 have become a research hotspot. Researchers hope that by developing such probes, they can non-invasively, intuitively, quantitatively, and dynamically display the expression and distribution characteristics of human ACE2, providing new methods for research on the mechanisms of COVID-19, prevention, diagnosis, and treatment, and the diagnosis of ACE2-expression-related tumors.
[0004] Because SARS-CoV-2 RBD can bind tightly to ACE2 through various interactions (hydrophobic and strong electrostatic interactions, including pp and cation-p), with the release of the RBD sequence, a radioactive iodine probe that can be used for in vivo, real-time, non-invasive imaging of ACE2 has emerged. 124 I-RBD was first reported, but factors such as deiodination and slow in vivo clearance limited its in-depth study; moreover, due to the complex structure of RBD, the site for I-124 labeling of RBD is still unclear; I-124 has low energy, long half-life, and high price, and is not a suitable radionuclide for nuclear medicine imaging. Since the S2 subunit of the SARS-CoV-2 virus is more conserved than the S1 subunit, researchers designed a pan-coronavirus inhibitor EK1 peptide derived from the HR2 domain of the SARS-CoV S2 subunit, and after conjugation with the chelating agent NOA, it was radiolabeled with Cu-64 to obtain […]. 64 Cu]-NOTA-EK1;[ 64Cu]-NOTA-EK1 effectively detected SARS-CoV-2 analogues in extrapulmonary lesions in mice, but peak uptake in the lesions was only achieved 8 hours after probe injection. Another class of probes based on the previously reported ACE2 peptide inhibitor DX600 was subsequently developed, such as […]. 68 HZ20 labeled Ga-NOTA-PEP4 and AlF-18 / Ga-68 / Cu-64 / Lu-177. 68 Ga-NOTA-PEP4 can specifically bind to ACE2 receptors in the heart, liver, lungs, and intestines. Ga-68 / Lu-177-labeled HZ20 exhibits specific uptake in tumors overexpressing ACE2. 18 F]AlF-DX600 showed high enrichment in the human urogenital system and moderate enrichment in the conjunctiva and nasal mucosa; however, there is currently no research to prove that this series of probes has the same binding site on ACE2 as SARS-CoV, or whether it can be used for research on the mechanism of COVID-19.
[0005] In summary, although seven radiolabeled ACE2-targeting radiopharmaceuticals have been reported, demonstrating specific binding to organs and tumors with high ACE2 expression, each still requires further improvement or in-depth research. Since ACE2 is expressed in many normal human tissues, the key to designing radiolabeled ACE2 agents is to enhance tumor cell uptake and retention, and accelerate in vivo metabolism. This necessitates the use of small molecular weight, high-affinity peptide fragments or drugs for radiolabeling.
[0006] Therefore, providing a radioactive probe based on the SARS-CoV series S protein sequence that targets angiotensin receptor II, exhibiting high affinity and specificity for angiotensin receptor II, while also possessing good in vivo bio-metabolic properties, has become a pressing technical challenge in this field. Summary of the Invention
[0007] One of the objectives of this invention is to provide a radioactive probe targeting angiotensin receptor II based on the S protein sequence of SARS-CoV series viruses. This radioactive probe exhibits high affinity and high specificity for angiotensin receptor II, and also has good in vivo bio-metabolic properties. It is a promising angiotensin receptor II PET imaging agent that can be used for lung cancer PET imaging and research on the mechanism of COVID-19.
[0008] The above-mentioned objective of this invention is achieved through the following technical solution:
[0009] A radioactive probe targeting angiotensin II based on the S protein sequence of SARS-CoV series viruses has the following structure:
[0010]
[0011] Where R is as follows:
[0012] Tyr-Lys-Tyr-Phe-Tyr-Leu-OH;
[0013] Ser-Asn-Asn-Leu-Asp-Ser-Lys-Val-Gly-Gly-Asn-Tyr-Asn-Tyr-Leu-Tyr-Arg-Leu-Ph e-OH;
[0014] or
[0015] Ser-Asn-Lys-Leu-Asp-Ser-Lys-Val-Ser-Gly-Asn-Tyr-Asn-Tyr-Leu-Tyr-Arg-Leu-Phe-OH.
[0016] Another objective of this invention is to provide a method for preparing the above-mentioned radioactive probe targeting angiotensin receptor II based on the S protein sequence of the SARS-CoV series viruses.
[0017] The above-mentioned objective of this invention is achieved through the following technical solution:
[0018] The preparation method of a radioactive probe targeting angiotensin receptor II based on the S protein sequence of SARS-CoV series viruses includes the following steps: dissolving the labeled precursor (A1 / A3 / A15) in sodium acetate buffer, and adding [ 68 The Ga]GaCl3 solution was mixed thoroughly, heated, and purified using a C18 column to obtain the structure shown above. 68 Ga-labeled radioactive probe targeting angiotensin receptor II based on the SARS-CoV-2 S protein sequence.
[0019] The reaction formula is as follows:
[0020]
[0021] Preferably, the preparation is as follows: 20 micrograms of the labeled precursor A1 are dissolved in 94 μL of 1.25 N sodium acetate buffer, the germanium-gallium generator is rinsed with 5 mL of high-purity 0.1 N hydrochloric acid solution, and the resulting 1 mL [ 68 A hydrochloric acid solution of GaCl3 was added to a sodium acetate solution of the precursor, mixed thoroughly, and reacted at 90°C for 10 min. The mixture was then purified using a C18 column, and the labeling rate was determined by radio-HPLC, yielding a radiochemical yield >99%. 68 Ga]Ga-A1.
[0022] Preferably, the preparation is as follows: 20 micrograms of the labeled precursor A3 are dissolved in 94 μL of 1.25 N sodium acetate buffer, the germanium-gallium generator is rinsed with 5 mL of high-purity 0.1 N hydrochloric acid solution, and the resulting 1 mL [ 68 A hydrochloric acid solution of GaCl3 was added to a sodium acetate solution of the precursor, mixed thoroughly, and reacted at 90°C for 10 min. The mixture was then purified using a C18 column, and the labeling rate was determined by radio-HPLC, yielding a radiochemical yield >99%. 68 Ga]Ga-A3.
[0023] Preferably, the preparation is as follows: 20 micrograms of the labeled precursor A15 are dissolved in 94 μL of 1.25 N sodium acetate buffer, the germanium-gallium generator is rinsed with 5 mL of high-purity 0.1 N hydrochloric acid solution, and the resulting 1 mL [ 68 A hydrochloric acid solution of GaCl3 was added to a sodium acetate solution of the precursor, mixed thoroughly, and reacted at 90°C for 10 min. The mixture was then purified using a C18 column, and the labeling rate was determined by radio-HPLC, yielding a radiochemical yield >99%. 68 Ga]Ga-A15.
[0024] Another objective of this invention is to provide the application of the above-mentioned radioactive probe targeting angiotensin receptor II based on the S protein sequence of the SARS-CoV series viruses in the preparation of lung cancer PET imaging and the mechanism of COVID-19.
[0025] The above-mentioned objective of this invention is achieved through the following technical solution:
[0026] Application of radioactive probes targeting angiotensin receptor II based on the S protein sequence of SARS-CoV series viruses in the preparation of lung cancer PET images and the mechanism of COVID-19.
[0027] A radioactive probe targeting angiotensin II based on the S protein sequence of SARS-CoV series viruses [ 68 Ga]Ga-A1 / A3 / A15 is a promising angiotensin receptor II PET imaging agent that can be used for lung cancer PET imaging and research on the mechanism of COVID-19.
[0028] Beneficial effects:
[0029] The radioactive probe targeting angiotensin II based on the S protein sequence of the SARS-CoV series viruses of this invention exhibits high affinity and high specificity for angiotensin II, and also has good in vivo bio-metabolic properties. It is a promising angiotensin II receptor PET imaging agent that can be used for lung cancer PET imaging and research on the mechanism of COVID-19.
[0030] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, but this does not imply any limitation on the scope of protection of the present invention. Attached Figure Description
[0031] Figure 1-1 The [prepared in Example 1 of this invention] 68 Radio-HPLC chromatogram of Ga]Ga-A1 labeled reaction solution.
[0032] Figure 1-2 The [prepared in Example 2 of this invention] 68 Radio-HPLC chromatogram of Ga]Ga-A3 labeled reaction solution.
[0033] Figure 1-3 The [prepared in Example 3 of this invention] 68 Radio-HPLC chromatogram of Ga]Ga-A15 labeled reaction solution.
[0034] Figure 2 This invention applies the biological distribution experiments in Examples 1-3. 68 Distribution diagram of Ga]Ga-A1 / A3 / A15 in mice bearing A549 tumors.
[0035] Figure 3 In the second application embodiment of the present invention, [ 68 Image of Ga-A1 / A3 / A15 in mice bearing A549 tumors via microPET / CT imaging. Detailed Implementation
[0036] Unless otherwise specified, the reagents and raw materials used in the preparation and detection methods described in the following examples and comparative examples are all commercially available products, and the equipment used is all common equipment.
[0037] Example 1
[0038] A radioactive probe targeting angiotensin II based on the S protein sequence of SARS-CoV series viruses [ 68 Preparation of Ga]Ga-A1
[0039] [ 68 Ga]Ga-A1 is the synthesis of gallium 68-2,2',2”-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid-(threonine-leucine-threonine-proline-threonine-leucine);
[0040] Synthesis reaction equation:
[0041]
[0042] Dissolve 20 μg of the labeled precursor A1 in 94 μL of 1.25 N sodium acetate buffer, rinse the germanium-gallium generator with 5 mL of high-purity 0.1 N hydrochloric acid solution, and then add 1 mL of the resulting solution. 68 A hydrochloric acid solution of GaCl3 was added to a sodium acetate solution of the precursor, mixed thoroughly, and reacted at 90°C for 10 min. The mixture was then purified using a C18 column, and the labeling rate was determined by radio-HPLC, yielding a radiochemical yield >99%. 68 Ga]Ga-A1;
[0043] As shown in Figure 1, this is the […] prepared in Example 1 of the present invention. 68 Radioactive HPLC chromatogram of Ga]Ga-A1 labeled reaction solution;
[0044] In the C18 column purification process described above, the C18 column is activated with 10 mL of ethanol and 10 mL of water. After loading the reaction solution onto the column, the column is rinsed with 10 mL of water and then washed with 0.3 mL of ethanol to obtain the product.
[0045] In the radio-HPLC determination described above, the first mobile phase is an aqueous solution of 0.1% trifluoroacetic acid, the second mobile phase is acetonitrile, and the gradient elution conditions are: 0 min, 95% of the first mobile phase; 0–20 min, 95%–0% of the first mobile phase; the flow rate of the mobile phase is 1 mL / min.
[0046] Example 2
[0047] A radioactive probe targeting angiotensin II based on the S protein sequence of SARS-CoV series viruses [ 68 Preparation of Ga]Ga-A3
[0048] [ 68 Ga]Ga-A3 is the synthesis of gallium 68-2,2',2”-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid-(serine-alanine-alanine-leucine-alanine-serine-leucine-valine-glycine-glycine-alanine-threonine-alanine-threonine-leucine-threonine-alanine-leucine-threonine-alanine-leucine-proline);
[0049] Synthesis reaction equation:
[0050]
[0051] Dissolve 20 μg of the labeled precursor A3 in 94 μL of 1.25 N sodium acetate buffer, rinse the germanium-gallium generator with 5 mL of high-purity 0.1 N hydrochloric acid solution, and then add 1 mL of the resulting solution. 68A hydrochloric acid solution of GaCl3 was added to a sodium acetate solution of the precursor, mixed thoroughly, and reacted at 90°C for 10 min. The mixture was then purified using a C18 column, and the labeling rate was determined by radio-HPLC, yielding a radiochemical yield >99%. 68 Ga]Ga-A3;
[0052] As shown in Figure 1, this is the […] prepared in Example 2 of the present invention. 68 Radioactive HPLC chromatogram of Ga-A3 labeled reaction solution;
[0053] In the C18 column purification process described above, the C18 column is activated with 10 mL of ethanol and 10 mL of water. After loading the reaction solution onto the column, the column is rinsed with 10 mL of water and then washed with 0.3 mL of ethanol to obtain the product.
[0054] In the radio-HPLC determination described above, the first mobile phase is an aqueous solution of 0.1% trifluoroacetic acid, the second mobile phase is acetonitrile, and the gradient elution conditions are: 0 min, 95% of the first mobile phase; 0–20 min, 95%–0% of the first mobile phase; the flow rate of the mobile phase is 1 mL / min.
[0055] Example 3
[0056] A radioactive probe targeting angiotensin II based on the S protein sequence of SARS-CoV series viruses [ 68 Preparation of Ga-A15
[0057] [ 68 Ga]Ga-A15 is the synthesis of gallium 68-2,2',2”-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid-(serine-alanine-leucine-leucine-alanine-serine-leucine-valine-serine-glycine-alanine-threonine-alanine-threonine-leucine-threonine-alanine-leucine-threonine-alanine-leucine-proline);
[0058] Synthesis reaction equation:
[0059]
[0060] Dissolve 20 μg of the labeled precursor A15 in 94 μL of 1.25 N sodium acetate buffer, rinse the germanium-gallium generator with 5 mL of high-purity 0.1 N hydrochloric acid solution, and then add 1 mL of the resulting solution. 68 A hydrochloric acid solution of GaCl3 was added to a sodium acetate solution of the precursor, mixed thoroughly, and reacted at 90°C for 10 min. The mixture was then purified using a C18 column, and the labeling rate was determined by radio-HPLC, yielding a radiochemical yield >99%. 68 Ga]Ga-A15;
[0061] As shown in Figure 1, this is the […] prepared in Example 3 of the present invention. 68 Radioactive HPLC chromatogram of Ga-A15 labeled reaction solution;
[0062] In the C18 column purification process described above, the C18 column is activated with 10 mL of ethanol and 10 mL of water. After loading the reaction solution onto the column, the column is rinsed with 10 mL of water and then washed with 0.3 mL of ethanol to obtain the product.
[0063] In the radio-HPLC determination described above, the first mobile phase is an aqueous solution of 0.1% trifluoroacetic acid, the second mobile phase is acetonitrile, and the gradient elution conditions are: 0 min, 95% of the first mobile phase; 0–20 min, 95%–0% of the first mobile phase; the flow rate of the mobile phase is 1 mL / min.
[0064] Application Example 1
[0065] [ 68 Biodistribution of Ga-A1 / A3 / A15 in mice bearing A549 tumors (lung cancer tumors)
[0066] The prepared [ 68 The Ga]Ga-A1 / A3 / A15 solution was diluted with physiological saline. Mice bearing A549 tumors (n=3) were injected with 60 μCi of the solution via the tail vein. The mice were sacrificed after 60 and 120 min, and the tissues of interest were collected to measure the radioactivity count.
[0067] The results of the biological distribution experiment show that: [ 68 Ga-A1 / A3 / A15 is highly uptaken in A549 tumors and is also uptaken in ACE2-expressing tissues throughout the mouse body (liver, spleen, gastrointestinal tract, joints, bone marrow, etc.); among which [ 68 Ga-A1 is primarily metabolized via the liver and intestines. 68 Ga]Ga-A3 / A15 is primarily metabolized by the kidneys; 68 The tumor / lung uptake ratio of Ga-Ga-A1 / A15 is relatively high, making it suitable for imaging primary lung cancer lesions.
[0068] like Figure 2 As shown, this is an experimental analysis of biological distribution in Example 1 of the present invention: [ 68 Distribution of Ga]Ga-A1 / A3 / A15 in mice bearing A549 tumors (lung cancer tumors).
[0069] Application Example 2
[0070] [ 68In vivo microPET imaging of Ga-A1 / A3 / A15 in mice bearing A549 tumors (lung cancer tumors).
[0071] The prepared [ 68 Ga]Ga-A1 / A3 / A15 solution was diluted with physiological saline, and 150 μCi of the drug solution was injected into the tail vein of mice bearing A549 tumors. MicroPET / CT imaging was performed 60 min later.
[0072] The results of the microPET imaging experiment show that: [ 68 Ga]Ga-A1 / A3 / A15 is highly uptaken in A549 tumors, among which [ 68 Ga]Ga-A3 uptake was the highest;
[0073] like Figure 3 As shown, this is an application embodiment 2 of the present invention. 68 Image of Ga-A1 / A3 / A15 in A549 tumor-bearing mice via microPET imaging.
[0074] The Ga-68-labeled radioactive probe targeting angiotensin II based on the S protein sequence of SARS-CoV series viruses of this invention is designed from the S protein sequence of SARS-CoV series viruses. Specifically, the polypeptide sequence of A1 is derived from amino acids 438-443 (R441F) of the β1' fold of the SARS-CoV virus S protein; the polypeptide sequence of A3 is derived from amino acids 438-456 of the α1'+β1' fold of the SARS-CoV virus S protein; and the polypeptide sequence of A15 is derived from amino acids 438-456 of the S protein of SARS-CoV-2 virus (Omicron B.1.1.529). Through experiments, the inventors found that the radioactive probe, modified from a portion of the S protein sequence of SARS-CoV series viruses, retains the affinity of SARS-CoV series viruses for the ACE2 receptor.
[0075] This invention relates to Ga-68-labeled radioactive probes targeting angiotensin II based on the S protein sequence of SARS-CoV series viruses. Key sites in the SARS-CoV series virus S protein sequence that bind to the ACE2 receptor (peptide sequences at the α1', β1', β2', η1', βc5, etc. folds of the S protein) are selected as targeting groups. These are linked to the chelating group NOA for easy Ga-68 labeling, and some amino acids are modified to enhance the hydrophobic interaction with the ACE2 receptor. After stability experiments, cell experiments, and in vivo animal evaluation, three radioactive probes with good metabolic properties and affinity for the ACE2 receptor were obtained. 68[Ga]Ga-A1 / A3 / A15. The polypeptide sequence of A1 is derived from amino acids 438-443 (R441F) of the β1' fold of the SARS-CoV virus S protein; the polypeptide sequence of A3 is derived from amino acids 438-456 of the α1'+β1' fold of the SARS-CoV virus S protein; and the polypeptide sequence of A15 is derived from amino acids 438-456 of the S protein of the SARS-CoV-2 virus (Omicron B.1.1.529).
[0076] Therefore, radioactive probes targeting angiotensin II based on the S protein sequence of SARS-CoV series viruses show high uptake in A549 tumors (human lung cancer tumors) and tissues expressing ACE2 receptors, and are expected to become PET imaging agents for lung cancer diagnosis or for research on the mechanism of COVID-19.
[0077] The above description is merely a preferred embodiment of the present invention, and therefore should not be construed as limiting the scope of the present invention. All equivalent changes and modifications made in accordance with the scope of the patent and the contents of the specification should still fall within the scope of the present invention.
Claims
1. Radioactive probes targeting angiotensin II based on the S protein sequence of the SARS-CoV series viruses are: [ 68 Ga]Ga-A1,[ 68 Ga]Ga-A3 and [ 68 Ga]Ga-A15, the structural formulas are as follows:
2. The method for preparing the radioactive probe targeting angiotensin receptor II based on the S protein sequence of SARS-CoV series viruses as described in claim 1, comprising the following steps: labeling the precursors 2,2',2”-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid-(tyrosine-lysine-tyrosine-phenylalanine-tyrosine-leucine), 2,2',2”-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid-(serine-asparagine-asparagine-leucine-aspartic acid-serine- Lysine-valine-glycine-glycine-asparagine-tyrosine-asparagine-tyrosine-leucine-tyrosine-arginine-leucine-phenylalanine) or 2,2',2”-(1,4,7-triazacyclononane-1,4,7-triyl)triacetic acid-(serine-asparagine-lysine-leucine-aspartic acid-serine-lysine-valine-serine-glycine-asparagine-tyrosine-asparagine-tyrosine-leucine-tyrosine-arginine-leucine-phenylalanine) dissolved in sodium acetate buffer, added [ 68 The Ga]GaCl3 solution was mixed thoroughly, heated, and purified using a C18 column to obtain the structure shown above. 68 Ga-labeled radioactive probes targeting angiotensin receptor II based on the S protein sequence of SARS-CoV series viruses.
3. The method for preparing a radioactive probe targeting angiotensin receptor II based on the S protein sequence of SARS-CoV series viruses according to claim 2, characterized in that: The preparation process is as follows: 20 μg of the labeled precursor A1 was dissolved in 94 μL of 1.25 N sodium acetate buffer; the germanium-gallium generator was rinsed with 5 mL of high-purity 0.1 N hydrochloric acid solution; and the resulting 1 mL [ 68 A hydrochloric acid solution of Ga]GaCl3 was added to a sodium acetate solution of the precursor, mixed thoroughly, and reacted at 90°C for 10 min. The mixture was then purified using a C18 column, and the labeling rate was determined by radio-HPLC, yielding a radiochemical yield >99%. 68 Ga]Ga-A1; The structural formula of A1 is as follows:
4. The method for preparing a radioactive probe targeting angiotensin receptor II based on the S protein sequence of SARS-CoV series viruses according to claim 2, characterized in that: The preparation is as follows: 20 μg of the labeled precursor A3 was dissolved in 94 μL of 1.25 N sodium acetate buffer, and the germanium-gallium generator was rinsed with 5 mL of high-purity 0.1 N hydrochloric acid solution. The resulting 1 mL... 68 A hydrochloric acid solution of Ga]GaCl3 was added to a sodium acetate solution of the precursor, mixed thoroughly, and reacted at 90°C for 10 min. The mixture was then purified using a C18 column, and the labeling rate was determined by radio-HPLC, yielding a radiochemical yield >99%. 68 Ga]Ga-A3; The structural formula of A3 is as follows:
5. The method for preparing a radioactive probe targeting angiotensin receptor II based on the S protein sequence of SARS-CoV series viruses according to claim 2, characterized in that: The preparation process is as follows: 20 μg of the labeled precursor A15 was dissolved in 94 μL of 1.25 N sodium acetate buffer; the germanium-gallium generator was rinsed with 5 mL of high-purity 0.1 N hydrochloric acid solution; and the resulting 1 mL [ 68 A hydrochloric acid solution of Ga]GaCl3 was added to a sodium acetate solution of the precursor, mixed thoroughly, and reacted at 90°C for 10 min. The mixture was then purified using a C18 column, and the labeling rate was determined by radio-HPLC, yielding a radiochemical yield >99%. 68 Ga]Ga-A15; The structural formula of A15 is as follows:
6. The use of the radioactive probe targeting angiotensin receptor II based on the S protein sequence of the SARS-CoV series viruses as described in claim 1 in the preparation of drugs for lung cancer PET imaging.