Developing agent of targeted CAIX receptor, developing agent labeled precursor and preparation method and application of developing agent and developing agent labeled precursor

Abstract

The invention provides a developing agent of a targeted CAIX receptor, a developing agent labeled precursor as well as a preparation method and application of the developing agent and the developing agent labeled precursor, and belongs to the field of radiopharmaceutical labeling. The developing agent and the developing agent labeled precursor are simple in preparation method, short in preparation time and high in radiochemical yield, have the advantages of good in-vivo and in-vitro stability, high specificity, high intake and the like, and can accurately and stably detect and locate tumor or inflammation parts. The CAIX in the tumor can be qualitatively diagnosed, a reliable basis is provided for accurate diagnosis and correct decision making in the stages of clinical staging, treatment decision making, curative effect monitoring and the like, and finally accurate diagnosis and treatment are achieved.

Description

Technical Field

[0001] The present invention belongs to the technical field of nuclear medicine, and in particular relates to an imaging agent targeting a CAIX receptor, an imaging agent labeling precursor, and a preparation method and application thereof. Background Art

[0002] CAIX, the full name of which is Carbonic anhydrase IX, is also called carbonic anhydrase IX in Chinese. As a transmembrane protein that is mainly overexpressed on the surface of tumor cells under hypoxic conditions, CAIX is closely related to the development of tumors, especially under hypoxic conditions. CAIX is specifically expressed in the hypoxic areas of tumor cells and is closely related to the regulation of the acidic microenvironment of tumors. This protein is regarded as an effective target for tumor imaging and treatment because of its specific high expression in tumors. The development of radioactive probes targeting CAIX is particularly important for the early diagnosis and treatment of tumors. By targeting CAIX, radioactive probes can provide more accurate tumor localization and evaluation, thereby enhancing the targetedness and effectiveness of treatment.

[0003] Therefore, based on the above background, the present invention designs, synthesizes and evaluates a series of compounds, and labels them with Ga-68 and LU-177 to obtain imaging agents targeting CAIX receptors. After successful radioactive labeling, they are evaluated in vitro and in vivo to detect the potential of quantitative detection of imaging agents. Through the synthesis and application of compounds and imaging agents targeting CAIX receptors, qualitative diagnosis of CAIX in tumors can be achieved, which can not only improve diagnostic efficiency, but also directly affect the selection of treatment methods and the evaluation of treatment effects. It provides a reliable basis for accurate diagnosis and correct decision-making in clinical staging, treatment decision-making, efficacy monitoring and other stages, and ultimately achieves precise diagnosis and treatment. Summary of the invention

[0004] The present invention provides an imaging agent targeting CAIX receptor, an imaging agent labeled precursor, and a preparation method and application thereof, which can realize the qualitative diagnosis of CAIX in tumors, provide a reliable basis for accurate diagnosis and correct decision-making in clinical staging, treatment decision-making, efficacy monitoring and other stages, and ultimately realize precise diagnosis and treatment.

[0005] The technical solution adopted by the present invention to achieve the above-mentioned purpose is: a developer labeling precursor targeting CAIX receptor, having a structure as shown in Formula 1, Formula 2 or Formula 3:

[0006]

[0007] or a pharmaceutically acceptable salt thereof, wherein: n is selected from an integer from 1 to 10;

[0008] X is selected from H, O, S, N or F.

[0009] The present invention discloses a method for preparing the above-mentioned developer labeling precursor, and the specific preparation steps are as follows:

[0010] (1) Synthesis of Compound 1

[0011] Compounds Boc-PEG4-COOH, HATU and DIPEA were dissolved in anhydrous DMF in sequence, and after stirring at room temperature for 0.5 h, compound AAZ dissolved in anhydrous DMF was added to the reaction system, and the reaction system was stirred at room temperature overnight. After the reaction was completed, a saturated NaHCO3 solution was added to the reaction system, and then EA was added for extraction, the organic phases were combined, and the organic phases were dried over anhydrous Na2SO4 in sequence, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain compound 1;

[0012] (2) Synthesis of Compound 2

[0013] Compound 1 was dissolved in a 4.0 M hydrogen chloride-dioxane solution and stirred at room temperature for 3 h. After the reaction was completed, the reaction system was concentrated under reduced pressure, ether was added for washing, and the remaining hydrochloric acid was removed by vacuum filtration to obtain compound 2;

[0014] (3) Synthesis of Compound 3

[0015] DOTA-tris (t-Buester), HATU and DIPEA were dissolved in anhydrous DMF in turn, and stirred at room temperature for 0.5 h. Compound 2 dissolved in anhydrous DMF was added to the reaction system and stirred at room temperature overnight. After the reaction process was completed, a saturated NaHCO3 solution was added to the reaction system, and then EA was added for extraction. The organic phases were combined, and the organic phases were dried over anhydrous Na2SO4 in turn, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain compound 3;

[0016] (4) Synthesis of imaging agent labeling precursor DOTA-PEG3-CAIXi

[0017] Compound 3 was dissolved in 6.0 M hydrochloric acid solution, and the reaction system was stirred at room temperature for 2 h. After the reaction process was completed, the reaction system was concentrated under reduced pressure, ether was added for washing, and the remaining hydrochloric acid was removed by vacuum filtration to obtain the imaging agent labeled precursor DOTA-PEG4-CAIXi.

[0018] The invention discloses an imaging agent targeting CAIX receptor, which is obtained by labeling the imaging agent labeling precursor with radioactive elements.

[0019] Furthermore, the radioactive element is 68 Ga and 177 Any of the following.

[0020] The present invention also discloses that the radioactive element is 68When Ga, the preparation steps of the developer are as follows:

[0021] (1) Inject 5 mL of 0.1 M hydrochloric acid solution into the germanium gallium generator to elute the 68 Eluent for GaCl3 ions;

[0022] (2) Add sodium acetate solution to 4 mL of the above eluent and adjust the pH value of the system to 4.0-4.2;

[0023] (3) adding the above-mentioned developer-labeled precursor solution, reacting at 90-100°C for 10 minutes, and cooling to room temperature; diluting with water to obtain a diluted reaction solution, and then separating with a C-18 column, filtering with a 70% ethanol aqueous solution to obtain 68 Ga-labeled PET imaging agent.

[0024] The present invention also discloses that the radioactive element is 177 When Lu, the preparation steps of the developer, the specific preparation steps are as follows:

[0025] (1) Add sodium acetate solution to 177 In LuCl3 solution, adjust the pH value of the system to 4.5;

[0026] (2) adding the above-mentioned developer-labeled precursor solution, reacting at 30-40°C for 10-20 minutes, and cooling to room temperature; diluting with water to obtain a diluted reaction solution, and then separating with a C-18 column, filtering with a 70% ethanol aqueous solution to obtain 177 Lu-labeled SPECT imaging agent.

[0027] The present invention also discloses the use of the imaging agent labeling precursor or the imaging agent in detecting diseases or symptoms associated with CAIX protein.

[0028] Furthermore, the disease or disorder associated with the CAIX protein includes tumor or inflammation.

[0029] Furthermore, the tumor includes any one or more of renal cancer, intestinal cancer, lung cancer, and breast cancer.

[0030] Compared with the prior art, the at least one technical solution adopted in the embodiments of this specification can achieve the following beneficial effects:

[0031] (1) The imaging agent labeled precursor compound of the present invention has a simple preparation method, a short preparation time, a high radiochemical yield, and has the advantages of good stability, high specificity, and high uptake both in vivo and in vitro, and can accurately and stably detect and locate tumors (kidney cancer, intestinal cancer, lung cancer, breast cancer) or inflammatory sites;

[0032] (2) The present invention synthesizes novel specific compounds for tumor tissues, and uses them as tumor imaging agents and therapeutic drugs for tumors with high CAIX expression in nuclear medicine;

[0033] (3) Radioactive elements synthesized by the present invention 68 Ga-labeled targeted CAIX radioactive probe for PET imaging, radioactive elements 177 Lu-labeled targeted CAIX radioactive probes are used for SPET imaging. Both can achieve qualitative diagnosis of CAIX in tumors, and then realize non-invasive and accurate quantification of CAIX in tumors, providing a reliable basis in clinical staging, treatment decision-making, efficacy monitoring and other stages, and ultimately achieving accurate diagnosis and treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on the drawings without paying creative work.

[0035] Figure 1 Mass spectra of precursors labeled with imaging agents;

[0036] Figure 2 is the HPLC spectrum of the imaging agent labeled precursor;

[0037] Figure 3 Radioactive probe 68 iTLC spectrum of Ga-DOTA-CAIXi;

[0038] Figure 4 Radioactive probe 177 HPLC spectrum of Lu-DOTA-CAIXi;

[0039] Figure 5 Radioactive probe 68 In vitro stability experimental analysis of Ga-DOTA-CAIXi in physiological saline;

[0040] Figure 6 Radioactive probe 68 In vitro stability analysis of Ga-DOTA-CAIXi in fetal bovine serum;

[0041] Figure 7 Radioactive probe 177 Analysis of in vitro stability experiment of Lu-DOTA-CAIXi in normal saline;

[0042] Figure 8 Radioactive probe 177In vitro stability analysis of Lu-DOTA-CAIXi in fetal bovine serum;

[0043] Fig. 9 Radioactive probe 68 PET imaging of Ga-DOTA-CAIXi;

[0044] Fig.10 Radioactive probe 177 SPECT image of Lu-DOTA-CAIXi. DETAILED DESCRIPTION

[0045] The embodiments of the present application are described in detail below with reference to the accompanying drawings.

[0046] The following describes the implementation methods of the present application through specific examples, and those skilled in the art can easily understand other advantages and effects of the present application from the contents disclosed in this specification. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. The present application can also be implemented or applied through other different specific implementation methods, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present application. It should be noted that, in the absence of conflict, the following embodiments and the features in the embodiments can be combined with each other. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in the field without making creative work belong to the scope of protection of the present application.

[0047] Example 1 Preparation of imaging agent labeled precursor targeting CAIX receptor

[0048] (1) Synthesis of Compound 1

[0049] In a 50 mL eggplant-shaped bottle, the compounds Boc-PEG4-COOH (1.3 eq), HATU (1.1 eq) and DIPEA (2.6 eq) were dissolved in 7 mL of anhydrous DMF. After the reaction system was stirred at room temperature for 0.5 h, the compound AAZ (1 eq) dissolved in 3 mL of anhydrous DMF was added to the reaction system, and the reaction system was stirred overnight at room temperature. After the reaction progress was monitored by TLC, a saturated NaHCO3 solution (2 × 30 mL) was added to the reaction system, and then EA (3 × 50 mL) was added for extraction, and the organic phases were combined. The organic phases were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography to obtain a solid powder compound 1.

[0050] (2) Synthesis of Compound 2

[0051] In a 50 mL eggplant-shaped bottle, compound 1 (1 eq) was added and dissolved in 10 mL of 4.0 M hydrogen chloride dioxane solution. The reaction system was stirred at room temperature for 3 h, and the reaction progress was monitored by TLC. The reaction system was concentrated under reduced pressure, washed with ether, and the remaining hydrochloric acid was removed by vacuum filtration to obtain compound 2.

[0052] (3) Synthesis of Compound 3

[0053] In a 50 mL eggplant-shaped bottle, the compounds DOTA-tris (t-Buester) (1.3 eq), HATU (1.1 eq) and DIPEA (2.6 eq) were dissolved in 7 mL of anhydrous DMF in turn. After the reaction system was stirred at room temperature for 0.5 h, compound 2 (1 eq) dissolved in 3 mL of anhydrous DMF was added to the reaction system, and the reaction system was stirred overnight at room temperature. After the reaction process was monitored by TLC, a saturated NaHCO3 solution (2 × 30 mL) was added to the reaction system, and then EA (3 × 50 mL) was added for extraction, and the organic phases were combined. The organic phases were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography to obtain a solid powder compound 3.

[0054] (4) Synthesis of imaging agent labeled precursor compound DOTA-PEG3-CAIXi

[0055] In a 50 mL eggplant-shaped bottle, compound 3 (1 eq) was dissolved in 6 mL 6.0 M hydrochloric acid solution, and the reaction system was stirred at room temperature for 2 h. After the reaction progress was monitored by TLC, the reaction system was concentrated under reduced pressure, washed with ether, and the remaining hydrochloric acid was removed by vacuum filtration to obtain the imaging agent labeled precursor compound DOTA-PEG4-CAIXi.

[0056] The synthetic route is as follows:

[0057]

[0058] The mass spectrum and HPLC spectrum of the imaging agent labeled precursor DOTA-PEG4-CAIXi targeting CAIX receptor are shown in Figure 1 and Figure 2 shown.

[0059] Example 2 Compound 68 Preparation of Ga-DOTA-CAIXi

[0060] (1) Inject 5 mL of 0.1 M hydrochloric acid solution into the germanium gallium generator to elute the 68 Eluent for GaCl3 ions;

[0061] (2) Add 0.375 mL of 1.5 M sodium acetate solution to 4 mL of the above eluent and adjust the pH value of the system to 4.2;

[0062] (3) Add 50 μL of the 1 mg / mL developer labeling precursor solution prepared in Example 1, react at 90° C. for 10 min, and then cool to room temperature; add 12 mL of sterile water to dilute the labeling system to obtain a diluted reaction solution, and then separate it using a C-18 column. The product is adsorbed onto the C-18 column, and 1.5 mL of ethanol aqueous solution (V 乙醇 :V 水 =70% / 30%) to produce the product from C 18 Eluted from the column to obtain 68 Ga-labeled PET imaging agent 68 Ga-DOTA-CAIXi.

[0063] The synthetic route is as follows:

[0064]

[0065] The product was evaluated by radio-thin layer chromatography (radio-TLC, developing solvent NH4Ac (1M) / MeOH = 1 / 1). Figure 3 ,from Figure 3 It can be seen that after purification 68 The radiochemical purity of Ga-DOTA-CAIXi is greater than 90% and maintains good stability.

[0066] Example 3 Compound 177 Preparation of Lu-DOTA-CAIXi

[0067] (1) Add 1.5M sodium acetate solution to 177 LuCl3 solution (370MBq), the pH value of the system was adjusted to 4.5;

[0068] (2) Add 50 μL of the 1 mg / mL developer labeled precursor solution prepared in Example 1, react at 40° C. for 20 min, and then cool to room temperature; dilute with water to obtain a diluted reaction solution, separate with a C-18 column, and filter through a 70% ethanol aqueous solution to obtain 177 Lu-labeled SPECT imaging agents 177 Lu-DOTA-CAIXi.

[0069] The synthetic route is as follows:

[0070]

[0071] The product was evaluated by radio-HPLC. Figure 4As shown, from Figure 4 It can be seen that after purification 177 The radiochemical purity of Lu-DOTA-CAIXi is greater than 90% and maintains good stability.

[0072] Example 4 Compound 68 Study on the Stability of Ga-DOTA-CAIXi

[0073] Saline stability

[0074] (1) Take three EP tubes and add 200 μL (0.74-2.96 MBq) of purified Ga-68 labeled radioactive probe to each EP tube;

[0075] (2) Add 800 μL of saline to each of the three EP tubes and shake thoroughly;

[0076] (3) incubating the mixture at room temperature for 0, 1, 2, and 3 h;

[0077] (4) Then 100 μL of the above mixture was taken from each EP tube and analyzed by radio-HPLC to evaluate the stability of the radioactive probe in physiological saline;

[0078] (5) The data of physiological saline stability were analyzed using GraphPad Prism 9.0 software.

[0079] Results Figure 5 As shown, 3h later 68 The radiochemical purity of Ga-DOTA-CAIXi is greater than 90% and maintains good stability.

[0080] In vitro fetal bovine serum stability

[0081] (1) Take three EP tubes and add 200 μL (0.74-2.96 MBq) of purified Ga-68 labeled radioactive probe to each EP tube;

[0082] (2) Add 800 μL of human serum to each of the three EP tubes and shake thoroughly;

[0083] (3) incubating the mixture at room temperature for 0, 1, 2, and 3 h;

[0084] (4) Then, 100 μL of the above mixture was taken from each EP tube and analyzed by radio-HPLC to evaluate the stability of the radioactive probe in human serum;

[0085] (5) The data of physiological saline stability were analyzed using GraphPad Prism 9.0 software.

[0086] Results Figure 6 As shown, 3h later 68 The radiochemical purity of Ga-DOTA-CAIXi is greater than 90% and maintains good stability.

[0087] Example 5 Compound 177 Study on the Stability of Lu-DOTA-CAIXi

[0088] Saline stability

[0089] (1) Take three EP tubes and add 200 μL (0.74-2.96 MBq) of purified Lu-177 labeled radioactive probe to each EP tube;

[0090] (2) Add 800 μL of saline to each of the three EP tubes and shake thoroughly;

[0091] (3) incubating the mixture at room temperature for 0, 1, 2, and 3 h;

[0092] (4) Then 100 μL of the above mixture was taken from each EP tube and analyzed by radio-HPLC to evaluate the stability of the radioactive probe in physiological saline;

[0093] (5) The data of physiological saline stability were analyzed using GraphPad Prism 9.0 software.

[0094] Results Figure 7 As shown, 3h later 177 The radiochemical purity of Lu-DOTA-CAIXi is greater than 90% and maintains good stability.

[0095] In vitro fetal bovine serum stability

[0096] (1) Take three EP tubes and add 200 μL (0.74-2.96 MBq) of purified Lu-177 labeled radioactive probe to each EP tube;

[0097] (2) Add 800 μL of human serum to each of the three EP tubes and shake thoroughly;

[0098] (3) incubating the mixture at room temperature for 0, 1, 2, and 3 h;

[0099] (4) Then, 100 μL of the above mixture was taken from each EP tube and analyzed by radio-HPLC to evaluate the stability of the radioactive probe in human serum;

[0100] (5) The data of physiological saline stability were analyzed using GraphPad Prism 9.0 software.

[0101] Results Figure 8 As shown, 3h later 177 The radiochemical purity of Lu-DOTA-CAIXi is greater than 90% and maintains good stability.

[0102] Example 6 Compound 68 Study on PET Imaging of Ga-DOTA-CAIXi

[0103] SPF grade Balb / c nude mice, female, 5 weeks old, were provided by Shanghai Jicui Biotechnology Co., Ltd. After two days of acclimatization in the animal room, OS-RC-2 human renal cancer cells were injected subcutaneously in the right axilla of the nude mice with an injection volume of 0.1 mL (1×10 8 cells / mL dispersed in PBS), and continued to be raised for 4-6 weeks after injection. When the solid tumor mass grew to 5-11 mm, it was used for imaging experiments. 100-200 μCi / 0.2 mL of 68 Ga-DOTA-CAIXi, imaging experiments were performed using small animal PET at 0.5, 1, and 2 h after injection.

[0104] According to the quantitative calculation of MicroPET / CT images, Fig. 9 As shown, in MicroPET / CT imaging, radioactive probes 68 Ga-DOTA-CAIXi showed a high radioactivity signal in human renal cancer OS-RC-2 tumors, but no obvious radioactivity signal accumulation in the lungs and abdomen (such as the stomach and intestines). The tumor and non-tumor areas were clearly distinguished, which means that the radioactivity probe 68 Ga-DOTA-CAIXi has the potential to be used for imaging human renal carcinoma primaries and their lung and intestinal metastases.

[0105] Example 7 Compound 177 Study on SPECT Imaging of Lu-DOTA-CAIXi

[0106] SPF grade Balb / c nude mice, female, 5 weeks old, were provided by Shanghai Jicui Biotechnology Co., Ltd. After two days of acclimatization in the animal room, OS-RC-2 human renal cancer cells were injected subcutaneously in the right axilla of the nude mice with an injection volume of 0.1 mL (1×10 8 cells / mL dispersed in PBS), and continued to be raised for 4-6 weeks after injection. When the solid tumor mass grew to 5-11 mm, it was used for imaging experiments. 250 μCi / 0.2 mL of 177 Lu-DOTA-CAIXi, imaging experiments were performed using small animal MicroSPCET 1, 2, and 4 h after injection.

[0107] According to the quantitative calculation of MicroSPCET / CT images, Fig.10 As shown, in MicroSPCET / CT imaging, the radioactive probe at 4 h after injection 177 The radioactivity signal of Lu-DOTA-CAIXi was higher in human renal cancer OS-RC-2 tumors, which means that the radioactive probe 177 Lu-DOTA-CAIXi has the potential to be used in radiotherapy of human renal cancer.

Claims

1. A CAIX receptor-targeting imaging agent labeled precursor, characterized in that: Having a structure as shown in Formula 1, Formula 2 or Formula 3: or a pharmaceutically acceptable salt thereof, wherein: n is an integer selected from 1 to 10; X is selected from H, O, S, N or F.

2. The imaging agent labeled precursor according to claim 1, characterized in that The specific preparation steps are as follows: (1) Synthesis of Compound 1 Compounds Boc-PEG4-COOH, HATU and DIPEA were dissolved in anhydrous DMF in sequence, and after stirring at room temperature for 0.5 h, compound AAZ dissolved in anhydrous DMF was added to the reaction system, and the reaction system was stirred at room temperature overnight. After the reaction was completed, a saturated NaHCO3 solution was added to the reaction system, and then EA was added for extraction, the organic phases were combined, and the organic phases were dried over anhydrous Na2SO4 in sequence, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain compound 1; (2) Synthesis of Compound 2 Compound 1 was dissolved in a 4.0 M hydrogen chloride-dioxane solution and stirred at room temperature for 3 h. After the reaction was completed, the reaction system was concentrated under reduced pressure, ether was added for washing, and the remaining hydrochloric acid was removed by vacuum filtration to obtain compound 2; (3) Synthesis of Compound 3 DOTA-tris (t-Buester), HATU and DIPEA were dissolved in anhydrous DMF in turn, and stirred at room temperature for 0.5 h. Compound 2 dissolved in anhydrous DMF was added to the reaction system and stirred at room temperature overnight. After the reaction process was completed, a saturated NaHCO3 solution was added to the reaction system, and then EA was added for extraction. The organic phases were combined, and the organic phases were dried over anhydrous Na2SO4 in turn, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain compound 3; (4) Synthesis of imaging agent labeling precursor DOTA-PEG3-CAIXi Compound 3 was dissolved in 6.0 M hydrochloric acid solution, and the reaction system was stirred at room temperature for 2 h. After the reaction process was completed, the reaction system was concentrated under reduced pressure, ether was added for washing, and the remaining hydrochloric acid was removed by vacuum filtration to obtain the imaging agent labeled precursor DOTA-PEG4-CAIXi.

3. An imaging agent targeting CAIX receptor, characterized in that: The imaging agent labeled precursor according to claim 1 is obtained by labeling with a radioactive element.

4. The developer according to claim 3, characterized in that The radioactive element is 68 Ga and 177 Any of the following.

5. The developer according to claim 4, characterized in that The radioactive element is 68 The specific preparation steps of Ga, developer are as follows: (1) Inject 5 mL of 0.1 M hydrochloric acid solution into the germanium gallium generator to elute the 68 Eluent for GaCl3 ions; (2) Add sodium acetate solution to 4 mL of the above eluent and adjust the pH value of the system to 4.0-4.2; (3) adding the developer labeling precursor solution of claim 1, reacting at 90-100° C. for 10 min, cooling to room temperature; diluting with water to obtain a diluted reaction solution, separating with a C-18 column, and filtering with a 70% ethanol aqueous solution to obtain 68 Ga-labeled PET imaging agent.

6. The developer according to claim 4, characterized in that The radioactive element is 177 The specific preparation steps of Lu, developer are as follows: (1) Add sodium acetate solution to 177 In LuCl3 solution, adjust the pH value of the system to 4.5; (2) adding the developer labeling precursor solution of claim 1, reacting at 30-40° C. for 10-20 min, and cooling to room temperature; diluting with water to obtain a diluted reaction solution, and then separating with a C-18 column, and filtering with a 70% ethanol aqueous solution to obtain 177 Lu-labeled imaging agent.

7. Use of the imaging agent labeled precursor according to claim 1 or the imaging agent according to any one of claims 3 to 4 in detecting diseases or disorders associated with CAIX protein.

8. The use according to claim 7, characterized in that The diseases or disorders associated with the CAIX protein include tumors or inflammation.

9. The use according to claim 8, characterized in that The tumor includes any one or more of renal cancer, intestinal cancer, lung cancer, and breast cancer.

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