Radiopharmaceutical labeled precursor targeting prostate specific membrane antigen, fluorine radiolabeled compound thereof and application of fluorine radiolabeled compound

Abstract

The invention discloses a class of radiopharmaceutical labeled precursors targeting prostate specific membrane antigens, the structure of the radiopharmaceutical labeled precursors is shown as the following: # imgabs0 #, a precursor reagent RESCA-PSMA-1802 targeting prostate specific membrane antigens is synthesized for the first time, the reagent can be labeled by using an 18F-Al method to prepare a positron imaging agent 18FAl-RESCA-PSMA-1802, and the reagent can be used for preparing the prostate specific membrane antigens. The polymer has good stability and biological activity in vivo and in vitro, has good targeting property on prostate cancer cells, can reflect tumor recurrence or metastasis conditions, and is very suitable for PET imaging.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and in particular relates to a radioactive drug labeling precursor targeting prostate specific membrane antigen and a fluorine radioactive labeling compound and application thereof. Background Art

[0002] Prostate-specific membrane antigen (PSMA), also known as folate hydrolase 1 (FOLH1), is a type of transmembrane glycoprotein, which is composed of an extracellular C-terminus, a transmembrane structure and a cytoplasmic N-terminus. The extracellular region accounts for 95% of the entire glycoprotein and is the main site for recognition by peptides, aptamers, small molecules and antibodies. PSMA is overexpressed on the surface of more than 90% of prostate cancer cells, and its expression level is higher in cancer cells of advanced and castration-resistant patients. As the malignancy of prostate cancer increases, the expression of PSMA also increases accordingly. Therefore, PSMA has become an important target for the diagnosis and treatment of prostate cancer. PSMA positron emission tomography (PET / CT) is used for diagnostic scanning to evaluate the expression of PSMA. Many studies have shown that compared with traditional scanning examinations, PSMAPET / CT has unique advantages in detecting prostate cancer lesions and can make more effective judgments in the early stage and stage of prostate cancer. In addition, PSMAPET / CT significantly improves diagnostic sensitivity and accuracy with its advantages of highly specific multimodal imaging. Currently, the US FDA has approved 68 Ga-PSMA11, 18 F-DCFPYL (Piflufolastat) and two positron-emitting molecular probes are used for the diagnosis of prostate cancer. They have shown strong diagnostic value in the diagnosis of clinical prostate recurrence and metastasis. 68 Ga-PSMA617, 68 Ga-PSMAI&T, etc. Among these PSMA probes, 68 The short half-life of Ga (68 minutes) makes it unsuitable for widespread commercialization. 68 The radioactivity of the Ga nuclide generator is limited (the common maximum is 50 millicuries), which is not suitable for large-scale clinical practice. At present, many domestic scientific research institutions have also applied for multiple patents, including 68The patent applications marked with Ga are as follows: CN117700479A, CN117700485A, CN117338960A, CN117209560A, CN117264012A, CN117069670A, CN116730983A, CN116283754A, CN116199736A, CN115572320A, CN115057801A, CN114 404619A, CN114014843A, CN113679857A, CN112851637A, CN112898270A, CN112321673A, CN112062695A, CN110305187A, CN110317151A, CN106075484A, etc. Although these drugs can be linked to therapeutic radionuclides, they are relatively short for PET imaging. 68 The half-life of Ga limits the development of large-scale clinical practice. 18 F-PSMA1007, [ 18 F]AlF-P16-093, etc. 18 Patent applications for F-labeled drugs include CN117263829A, CN114671806A, CN112961173A, CN112675311A, CN112190722A, CN111548305A, CN109160898A, CN109160896A, CN107353323A, CN110938041A, etc. The preparation of these drugs mostly requires relatively harsh reaction conditions and complicated reaction and purification processes, such as high temperature, strong alkali or strong acid hydrolysis, separation using high pressure liquid chromatography, etc. Therefore, clinical promotion is subject to certain restrictions.

[0003] Patent application with publication number WO2016065435A2 discloses preparation of PSMA inhibitor H3L27-MPAA-PSMA by room temperature labeling. 18 F labeled product Al 18 F-L27-PSMA has a high radioactivity concentration in the liver, intestines and muscles, which can cause radiation damage to normal organs such as the liver and intestines. At the same time, the increased muscle uptake causes a higher background uptake, which reduces the signal-to-noise ratio and is not conducive to clinical transformation and application. Summary of the invention

[0004] The object of the present invention is to provide a class of radioactive drug labeling precursors targeting prostate specific membrane antigen.

[0005] Another object of the present invention is to provide a fluorine radioactive labeled compound prepared from the radioactive drug labeled precursor targeting prostate specific membrane antigen.

[0006] The third object of the present invention is to provide a type of radiolabeled compound used in the preparation of positron-emitting prostate cancer imaging agents.

[0007] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0008] In the first aspect of the present invention, a radioactive drug labeling precursor targeting prostate-specific membrane antigen is provided, the structure of which is shown below:

[0009]

[0010] The second aspect of the present invention provides a fluorine radioactive labeled compound, which is prepared by the radioactive drug labeled precursor targeting prostate-specific membrane antigen and a radioactive nuclide, wherein the radioactive nuclide is selected from 18 F.

[0011] The structure of the fluorine radioactive labeled compound is selected from one of the following structures:

[0012]

[0013] The third aspect of the present invention provides a method for preparing the fluorine radioactive labeled compound, comprising the following steps:

[0014] The radioactive drug labeling precursor targeting prostate-specific membrane antigen is dissolved in a buffer solution, and an acetic acid / sodium acetate buffer solution containing aluminum chloride is added. 18 F ion in sterile sodium chloride injection, react at room temperature for 5 to 20 minutes (preferably 10 to 15 minutes);

[0015] Separating and purifying by high pressure liquid phase and solid phase extraction, diluting with sodium ascorbate solution and sterilizing to obtain the fluorine radioactive labeled compound;

[0016] Alternatively, the fluorine radioactive labeled compound is obtained by separation and purification through solid phase extraction, dilution with sterile water, and sterilization.

[0017] The buffer solution is an acetic acid / sodium acetate buffer solution with a pH of 4.0-6.0 (preferably 4.5, 5) and a concentration of 0.05 mmol / L to 1 mol / L (preferably 0.2 mol / L).

[0018] The acetic acid / sodium acetate buffer solution containing aluminum chloride: the concentration of the aluminum chloride is 5-15 mmol / L (preferably 5, 10 mmol / L); the pH is 4.0-6.0 (preferably 4.5, 5.0).

[0019] The step of separation and purification by solid phase extraction is as follows: adding sterile water for injection to the solution after the reaction is completed, separation and purification by solid phase extraction, flushing the solid phase extraction chromatographic column with sterile water for injection, and then eluting the product on the solid phase extraction chromatographic column into a transfer bottle with 50% ethanol solution.

[0020] The solid phase extraction chromatographic column is selected from C-18, tC-18, HLB column and the like.

[0021] The steps of separation and purification by high pressure liquid phase and solid phase extraction in sequence are as follows: purification by HPLC (mobile phase is 30% acetonitrile aqueous solution, wavelength is 220nm, flow rate is 4mL / min, 25cm×10mm C18 chromatographic column), collecting the product with a radioactive retention time of 12-14min into sterile water, separating and concentrating with a Light-C18 solid phase extraction column, rinsing the solid phase extraction column with sterile water for injection, and eluting the product on the solid phase extraction column into a transfer bottle with a 50% ethanol solution.

[0022] The sodium ascorbate solution is prepared by dissolving sodium ascorbate in water, with a concentration of 1 to 1500 mg / mL (preferably 12.5 mg / mL).

[0023] The sterilization is performed using a 0.22 micron sterilization filter membrane.

[0024] The undecay-corrected radiochemical yield of the fluorine radioactive labeled compound is 10-65% (preferably 55%, 60%, 65%), and the radioactive specific activity is 1-100 GBq / umol (preferably 3.46 GBq / umol, 65.5 GBq / umol, 89.3 GBq / umol).

[0025] The fourth aspect of the present invention provides a use of the fluorine radioactive labeled compound in the preparation of a positron emitting prostate cancer imaging agent.

[0026] The fifth aspect of the present invention provides a use of the fluorine radioactive labeled compound in the preparation of a positron-emitting molecular probe specifically targeting prostate-specific membrane antigen PSMA.

[0027] Due to the adoption of the above technical solution, the present invention has the following advantages and beneficial effects:

[0028] The present invention provides a class of radioactive drug labeled precursors RESCA-PSMA-1802 targeting prostate specific membrane antigen, and adopts18 Preparation of positron imaging agents by radioactive labeling with F-Al labeling method at room temperature 18 FAl-RESCA-PSMA-1802, due to 18 The physical half-life of F (110 min) is greater than 68 The physical half-life of Ga (68min) can meet the routine distribution of clinical drugs.

[0029] The fluorine radioactive labeling compound of the invention has simple preparation, low energy consumption, high labeling rate and good in vivo and in vitro stability. After the molecular probe is incubated in fetal bovine serum for 2 hours, the prototype retention rate is greater than 95%.

[0030] The present invention synthesized for the first time a precursor reagent RESCA-PSMA-1802 targeting prostate-specific membrane antigen (PSMA), which can be used 18 F-Al method was used to prepare positron imaging agents by labeling at room temperature 18 FAl-RESCA-PSMA-1802 has good stability and biological activity in vivo and in vitro, has good targeting to prostate cancer cells, can reflect tumor recurrence or metastasis, and is very suitable for PET imaging.

[0031] In the preparation process of the radioactive labeled compound of the present invention, the radioactive labeling is fast, efficient and low in energy consumption, the target compound is convenient and simple to separate, the radioactive product has a very high radioactive specific activity, and the label has the value of being used for clinical examination and diagnosis.

[0032] The radioactive labeled compound of the invention has mild preparation conditions, high labeling rate, good biological performance and better in vivo stability. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 This is a schematic diagram of the mass spectrum of compound RESCA-PSMA-1801.

[0034] Figure 2 This is a schematic diagram of the mass spectrum of compound RESCA-PSMA-1802.

[0035] Figure 3 yes 18 FAl-RESCA-PSMA-1801 and 18 HPLC profile of FAl-RESCA-PSMA-1802 after incubation in fetal bovine serum for 2 h.

[0036] Figure 4 yes 18 In vivo distribution of FAl-RESCA-PSMA-1801 in tumor model LNCap mice at 10, 30, 60, and 120 minutes.

[0037] Figure 5 yes 18 In vivo distribution of FAl-RESCA-PSMA-1802 in tumor model 22RV1 mice at 30, 60, 90, and 120 minutes. DETAILED DESCRIPTION

[0038] In order to explain the present invention more clearly, the present invention is further described below in conjunction with preferred embodiments. It should be understood by those skilled in the art that the following specific description is illustrative rather than restrictive, and should not be used to limit the scope of protection of the present invention.

[0039] 2,2′-(((1R,2R)-2-((carboxymethyl)(4-(2-oxo-2-(2,3,5,6-tetrafluorophenoxy)ethyl)benzyl)amino)cyclohexyl)azepinediyl)diacetic acid, (((S)-5-(6-aminohexanamido)-1-carboxypentyl)carbamoyl)-L-glutamic acid and (((S)-5-amino-1-carboxypentyl)carbamoyl)-L-glutamic acid were purchased from Probe Biotechnology Co., Ltd., Nanchang, Jiangxi Province.

[0040] Example 1

[0041]

[0042] 2,2'-(((1R,2R)-2-((carboxymethyl)(4-(2-oxo-2-(2,3,5,6-tetrafluorophenoxy)ethyl)benzyl)amino)cyclohexyl)azepinediyl)diacetic acid (11.6 mg, 20 μmol, 1 equivalent) was dissolved in 1 mL of dimethyl sulfoxide and 1 mL of 0.05 M sodium bicarbonate mixed solution, (((S)-5-(6-aminohexylamido)-1-carboxypentyl)carbamoyl)-L-glutamic acid (8.7 mg, 20 μmol, 1 equivalent) was added, and the mixed solution was stirred at room temperature overnight. The reaction solution was purified by Semi-HPLC (mobile phase: A 0.1% trifluoroacetic acid water, B acetonitrile; 20% B 20 min, flow rate 4 mL / min, C18-B, 250 mm×10 mm, 5 μm, Morhchem Technologies Inc., USA; retention time t R 10-12 minutes), to obtain 14.2 mg of white solid RESCA-PSMA-180 (yield: 25%); Figure 1 This is a schematic diagram of the mass spectrum of compound RESCA-PSMA-1801. MS (ESI) theoretical molecular weight [M+H] + 850.40, measured molecular weight 851.0 [M+H] + .

[0043] Example 2

[0044]

[0045] 2,2'-(((1R,2R)-2-((carboxymethyl)(4-(2-oxo-2-(2,3,5,6-tetrafluorophenoxy)ethyl)benzyl)amino)cyclohexyl)azepinediyl)diacetic acid (11.6 mg, 20 μmol, 1 equivalent) was dissolved in 1 mL of dimethyl sulfoxide and 1 mL of 0.05 M sodium bicarbonate mixed solution, ((((S)-5-amino-1-carboxypentyl)carbamoyl)-L-glutamic acid (6.4 mg, 20 μmol, 1 equivalent) was added, and the mixed solution was stirred at room temperature overnight. The reaction solution was purified by Semi-HPLC (mobile phase: A 0.1% trifluoroacetic acid water, B acetonitrile; 20% B 20 min, flow rate 4 mL / min, C18-B, 250 mm×10 mm, 5 μm, Morhchem Technologies Inc., USA; retention time t R 8-10 minutes), to obtain 23.1 mg of white solid RESCA-PSMA-180 (yield: 21%); Figure 2 This is a schematic diagram of the mass spectrum of compound RESCA-PSMA-1802. MS (ESI) theoretical molecular weight [M+H] + 737.31, measured molecular weight 738.3 [M+H] + .

[0046] Example 3

[0047]

[0048] 100 μg of RESCA-PSMA-1801 prepared in Example 1 was dissolved in 500 μl of acetic acid / sodium acetate buffer solution (pH 4.5, 0.2 mol / L), and then 5 μl of 10 mmol / L aluminum chloride in acetic acid / sodium acetate buffer solution (pH 4.5, 0.2 mol / L) was added and transferred to a plate containing 18F ion (740MBq) was added to a reaction bottle of 0.2mL sterile sodium chloride injection, and the reaction was shaken at room temperature for 10 minutes. 10mL sterile water for injection was added to the reaction solution, and the reaction was separated and purified by solid phase extraction. The solid phase extraction chromatographic column used a C-18 column. After the solid phase extraction chromatographic column was rinsed with 10mL sterile water for injection (commercially purchased), the product on the solid phase extraction chromatographic column was eluted into a transfer bottle with 2mL 50% ethanol solution. 8mL of aqueous solution containing 100mg sodium ascorbate was added for dilution, and sterilized with a 0.22μm sterilizing filter membrane to obtain 407MBq of radiolabeled compound. 18 FAl-RESCA-PSMA-1801. The undecay-corrected radiochemical yield was 55.0% and the specific radioactivity was 3.46 GBq / umol.

[0049] The radionuclide 18 Preparation of F:

[0050] Using a 10 MV accelerator through a nuclear reaction 18 O(p,n) 18 F Production 18 F, the target beam current is 50μA, and the bombardment for 10min generates 3.7GBq 18 F; adsorbed by anion exchange solid phase extraction column QMA, eluted with 0.5 mL of sodium chloride aqueous solution 18 F ions into the reaction bottle.

[0051] Establishment of tumor model LNCap mice: Human prostate cancer cells (LNCaP cell line) with high expression of PSMA were resuscitated, CHO D02 medium was added to T75 flasks, cells were inoculated and placed in a 37°C 5% CO2 incubator for culture. When the cell density reached about 85% of the bottom of the culture dish, the cells were collected by centrifugation, and the cells were diluted and resuspended in sterile PBS. The cells were counted, and the corresponding volume of cell suspension was aspirated according to the inoculation density of 500,000 cells per mouse, and stored on ice and transferred to the animal operation room.

[0052] Select 5-week-old NCG mice (purchased from Heyuan Biotechnology (Shanghai) Co., Ltd.), fix the mice, use a pipette to blow the cell suspension evenly before injecting cells, use a sterile syringe to absorb the cell suspension, and slowly inject the cell suspension containing the target cell amount into the subcutaneous position of the mouse armpit according to the liquid volume of 100-150 μl per mouse. After the injection, observe the vital signs and movement of the mice. When the tumor volume is greater than 300mm 3 It was then used in subsequent small animal PET / CT imaging experiments.

[0053] The LNCap tumor model was randomly divided into two groups, with 10 mice in each group. One group was used for static imaging for 10, 30, 60, and 120 min (each mouse was injected with approximately 5.55 MBq of imaging agent). 18 FAl-RESCA-PSMA-1801), and another group for blocking experiments (after injection of imaging agents 18 About 200 μg of PSMA 11 was injected as a blocking agent 5 minutes before FAl-RESCA-PSMA-1801, and static scanning of small animal PET / CT was performed 60 minutes after the injection of the imaging agent.

[0054] The results show that 18 The maximum uptake value SUVmax of FAl-RESCA-PSMA-1801 in tumor model mice was 0.5 (60 min), and the SUVmax of blocking imaging was 0.1 (60 min). 18 FA1-RESCA-PSMA-1801 is a positron emission tomography (PET) molecular probe specifically targeting prostate-specific membrane antigen (PSMA).

[0055] Figure 4 yes 18 The in vivo distribution diagram of FAl-RESCA-PSMA-1801 in tumor model LNCap mice at 10, 30, 60, and 120 minutes. It can be seen that 18 FAl-RESCA-PSMA-1801 is mainly cleared by liver metabolism. Over time, the uptake of the molecular probe in the liver first increases and then decreases, and then concentrates in the intestine. The uptake in the tumor site reaches the highest level 30 minutes after the injection of the imaging agent, and then gradually decreases, proving that 18 FAl-RESCA-PSMA-1801 has a shorter residence time at the tumor site and is cleared faster.

[0056] Example 4

[0057]

[0058] Dissolve 50 μg of RESCA-PSMA-1802 in 500 μl of acetic acid / sodium acetate buffer solution (pH 5.0, 0.2 mol / L), add 5 μl of 10 mmol / L aluminum chloride in acetic acid / sodium acetate buffer solution (pH 5, 0.2 mol / L), and transfer to a 18F ion (7.4GBq) was added to a reaction bottle of 0.5mL sterile sodium chloride injection, and the reaction was shaken at room temperature for 15 minutes. It was purified by HPLC (mobile phase was 30% acetonitrile aqueous solution, wavelength was 220nm, flow rate was 4mL / min, 25cm×10mm C18 chromatographic column), and the product with a radioactive retention time of 12-14min was collected into 30mL sterile water, and then separated and concentrated using a Light-C18 solid phase extraction column. After rinsing the solid phase extraction column with 10mL sterile injection water (commercially purchased), the product on the solid phase extraction column was rinsed into a transfer bottle with 2mL 50% ethanol solution. 8mL of aqueous solution containing 100mg sodium ascorbate was added for dilution, and sterilized with a 0.22μm sterilizing filter membrane to obtain 4.44GBq of radiolabeled compound. 18 FAl-RESCA-PSMA-1802. The undecay-corrected radiochemical yield was 60.0% and the specific radioactivity was 65.5 GBq / umol.

[0059] Establishment of tumor model 22RV1 mice: Human prostate cancer cells (22RV1 cell line) with high expression of PSMA were resuscitated, CHO D02 medium was added to T75 flasks, cells were inoculated and placed in a 37°C 5% CO2 incubator for culture. When the cell density reached about 85% of the bottom of the culture dish, the cells were collected by centrifugation, and the cells were diluted and resuspended in sterile PBS. The cells were counted, and the corresponding volume of cell suspension was aspirated according to the inoculation density of 500,000 cells per mouse, and stored on ice and transferred to the animal operation room.

[0060] Select 5-week-old Balb / c nude mice (purchased from Heyuan Biotechnology (Shanghai) Co., Ltd.), fix the mice, use a pipette to blow the cell suspension evenly before injecting cells, use a sterile syringe to absorb the cell suspension, and slowly inject the cell suspension containing the target cell amount into the subcutaneous position of the mouse armpit according to the liquid volume of 100-150 μl per mouse. After the injection, observe the vital signs and movement of the mice. When the tumor volume is greater than 300mm 3 It was then used in subsequent small animal PET / CT imaging experiments.

[0061] The 22RV1 tumor model was randomly divided into two groups, with 10 mice in each group. One group was used for static imaging for 10, 30, 60, and 120 min (each mouse was injected with about 7.40 MBq of imaging agent). 18 FAl-RESCA-PSMA-1802), and another group for blocking experiments (after injection of imaging agents 18 About 150 μg of PSMA 11 was injected as a blocking agent 5 minutes before FAl-RESCA-PSMA-1802, and a static scan of small animal PET / CT was performed 60 minutes after the injection of the imaging agent.

[0062] The results show that 18 The maximum uptake value SUVmax of FAl-RESCA-PSMA-1802 in tumor model mice was 0.9 (60 min), and the SUVmax of blocking imaging was 0.1 (60 min). 18 FA1-RESCA-PSMA-1802 is a positron emission tomography (PET) molecular probe specifically targeting prostate-specific membrane antigen (PSMA).

[0063] Figure 5 yes 18 The in vivo distribution diagram of FAl-RESCA-PSMA-1802 in tumor model 22RV1 mice at 30, 60, 90, and 120 minutes. It can be seen that 18 FAl-RESCA-PSMA-1802 is mainly cleared by renal metabolism. Over time, the uptake of the molecular probe in the kidney first increases and then decreases. The uptake of the molecular probe in the tumor site reaches a peak at 60 minutes and does not change over time in the 2-hour imaging experiment. 18 FAl-RESCA-PSMA-1801, 18 FAl-RESCA-PSMA-1802 is a positron-emitting prostate cancer imaging agent that is more suitable for clinical use.

[0064] Example 5

[0065] 0.74MBq 18 FAl-RESCA-PSMA-1801 or 0.74MBq 18 FAl-RESCA-PSMA-1802 was added to fetal bovine serum, incubated at room temperature for 2 h, and analyzed by HPLC. 18 HPLC conditions of FAl-RESCA-PSMA-1801: Mobile phase: A 0.1% trifluoroacetic acid water, B acetonitrile; 17% B 15 min, flow rate 1 mL / min; C18-B, 150 mm×4.6 mm, 5 μm, Morhchem Technologies Inc., USA; 18 HPLC conditions of FAl-RESCA-PSMA-1802: 17% B 15 min, flow rate 1 mL / min; C18-B, 150 mm × 4.6 mm, 5 μm, Morhchem Technologies Inc., USA; Figure 3 yes 18 FAl-RESCA-PSMA-1801 and 18HPLC profile of FAl-RESCA-PSMA-1802 after incubation in fetal bovine serum for 2 h. 18 FAl-RESCA-PSMA-1801 and 18 The retention time of FAl-RESCA-PSMA-1802 was 9.9 minutes and 8.8 minutes respectively. After the molecular probe was incubated in fetal bovine serum for 2 hours, the prototype retention rate was greater than 95%. This shows that these two positron molecular probes have good in vitro stability. 18 FAl-RESCA-PSMA-1802 and 18 FAl-RESCA-PSMA-1801 can be used as a stable and specific positron-emitting molecular probe targeting prostate-specific membrane antigen PSMA for further research and discussion.

[0066] Example 6

[0067] 100 μg of RESCA-PSMA-1802 was dissolved in 500 μl of acetic acid / sodium acetate buffer solution (pH 5.0, 0.2 mol / L), and then 5 μl of 10 mmol / L aluminum chloride in acetic acid / sodium acetate buffer solution (pH 4.5, 0.1 mol / L) was added and transferred to a plate containing 18 F ion (18.5GBq) was added to a reaction bottle of 0.5mL sterile sodium chloride injection solution, and the reaction was shaken at room temperature for 15 minutes. 10mL sterile injection water was added to the reaction solution, and the solid phase extraction separation and purification was performed. The solid phase extraction chromatographic column used an HLB column. After the solid phase extraction chromatographic column was rinsed with 10mL sterile injection water (commercially purchased), the product on the solid phase extraction chromatographic column was eluted into a transfer bottle with 2mL 50% ethanol solution. 8mL sterile water was added for dilution, and sterilized with a 0.22μm sterilizing filter membrane to obtain 12.1GBq of radioactive labeled compound. 18 FAl-RESCA-PSMA-1802. The unattenuated radiochemical yield was 65.0%, the total synthesis time was 32 minutes, and the corrected radiochemical yield was 79.5%. The specific radioactivity was 89.3 GBq / umol.

[0068] The above is only a preferred embodiment of the present invention, and does not limit the present invention in any form. Although the present invention has been disclosed as a preferred embodiment, it is not used to limit the present invention. Any technician familiar with this patent can make some changes or modify the technical contents suggested above into equivalent embodiments without departing from the scope of the technical solution of the present invention. However, any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the present invention without departing from the content of the technical solution of the present invention still fall within the scope of the solution of the present invention.

Claims

1. A radioactive drug labeled precursor targeting prostate specific membrane antigen, characterized in that: The structure is as follows:

2. A fluorine radioactive labeled compound, characterized in that The invention is prepared by the radioactive drug labeling precursor targeting prostate-specific membrane antigen according to claim 1 and a radionuclide, wherein the radionuclide is selected from 18 F; The structure of the fluorine radioactive labeled compound is shown below:

3. A method for preparing a fluorine radioactive labeled compound according to claim 2, characterized in that: The following steps are involved: The radioactive drug labeling precursor targeting prostate-specific membrane antigen is dissolved in a buffer solution, and an acetic acid / sodium acetate buffer solution containing aluminum chloride is added. 18 F ion in sterile sodium chloride injection, react at room temperature for 5 to 20 minutes; Separating and purifying by high pressure liquid phase and solid phase extraction, diluting with sodium ascorbate solution and sterilizing to obtain the fluorine radioactive labeled compound; Or, separation and purification by solid phase extraction, dilution with sterile water, and sterilization to obtain the fluorine radioactive labeled compound; The buffer solution is an acetic acid / sodium acetate buffer solution with a pH of 4.0-6.0 and a concentration of 0.05 mmol / L to 1 mol / L; The acetic acid / sodium acetate buffer solution containing aluminum chloride has a concentration of 5 to 15 mmol / L and a pH of 4.0 to 6.

0.

4. The method for preparing a fluorine radioactive labeled compound according to claim 3, characterized in that: The step of separation and purification by solid phase extraction is as follows: adding sterile water for injection to the solution after the reaction is completed, separation and purification by solid phase extraction, flushing the solid phase extraction chromatographic column with sterile water for injection, and then eluting the product on the solid phase extraction chromatographic column into a transfer bottle with 50% ethanol solution.

5. The method for preparing a fluorine radioactive labeled compound according to claim 3, characterized in that: The steps of separation and purification by high pressure liquid phase and solid phase extraction in sequence are as follows: purification by HPLC, collecting the product with a radioactive retention time of 12-14 minutes into sterile water, separating and concentrating with a Light-C18 solid phase extraction column, flushing the solid phase extraction column with sterile water for injection, and eluting the product on the solid phase extraction column into a transfer bottle with a 50% ethanol solution.

6. The method for preparing a fluorine radioactive labeled compound according to claim 3, characterized in that: The sodium ascorbate solution is prepared by dissolving sodium ascorbate in water with a concentration of 1 to 1500 mg / mL; The undecay-corrected radiochemical yield of the fluorine radioactive labelled compound is 10-65%, and the radioactive specific activity is 1-100 GBq / umol.

7. Use of the fluorine radioactive labeled compound according to claim 2 in the preparation of a positron emitting prostate cancer imaging agent.

8. Use of the fluorine radioactive labeled compound according to claim 2 in the preparation of a positron-emitting molecular probe specifically targeting prostate-specific membrane antigen (PSMA).

Images