A compound targeting CAIX and FAP, its radionuclide marker, preparation method and application

Abstract

The present invention discloses a compound targeting CAIX and FAP, a radionuclide label thereof, a preparation method, and applications thereof, belonging to the field of nuclear medicine technology. The compound targeting CAIX and FAP of the present invention, or a salt thereof, has a structure shown in Formula I, and its radionuclide label has a structure shown in Formula II. The preparation method of the compound of Formula I comprises: reacting Compound 3 with Compound 10 to produce Compound 11; and then reacting Compound 11 with Compound 12 to produce the compound of Formula I. The preparation method of the radionuclide label of the present invention comprises: reacting the compound of Formula I with a radionuclide salt to produce the radionuclide label of Formula II. The present invention discloses the use of compounds of Formula I and Formula II in the preparation of products for detecting and / or monitoring cells and / or tissues expressing FAP and CAIX receptors. The compounds of the present invention or their radionuclide labels are used for the diagnosis and / or treatment of tumors expressing FAP and CAIX receptors, and have advantages such as high affinity, high T / NT ratios, and rapid renal clearance.

Description

Technical Field

[0001] The present invention belongs to the field of nuclear medicine technology, and in particular relates to a compound targeting CAIX and FAP, a radionuclide marker thereof, a preparation method and an application thereof. Background Art

[0002] Cancer, also known as malignant tumor, is a heterogeneous disease that forms in an extremely complex microenvironment. According to the latest statistics, there were 19,976,499 new cases of malignant tumors worldwide in 2022, an increase of nearly 700,000 people compared to 2020. Among them, the malignant tumor with the highest incidence rate was lung cancer with 2,480,675 (12.4%), surpassing breast cancer again. The 2nd to 6th place in incidence rate were breast cancer, colorectal cancer, prostate cancer, gastric cancer, and liver cancer, respectively. The tumor microenvironment plays an important role in the occurrence, development, metastasis and drug sensitivity of tumors. The inside of the tumor is like a highly organized ecosystem, which contains not only tumor cells but also a rich variety of immune cells, tumor-associated fibroblasts (CAFs), endothelial cells (ECs) and other cell types. Fibroblast Activation Protein (FAP) is a membrane-bound serine protease of the dipeptidyl peptidase 4 (DPP4) family that is overexpressed in CAFs and is overexpressed in approximately 90% of epithelial tumors. Based on the fact that FAP protein is lowly expressed in normal tissues but highly expressed in the tumor microenvironment, nuclear medicine diagnosis and treatment targeting FAP have developed rapidly in recent years. 68 Ga-FAPI-04 has been used in the diagnosis of up to 28 types of tumors, including sarcoma, esophageal cancer, breast cancer, and lung cancer, but it has the disadvantages of low accuracy and low sensitivity.

[0003] Carbonic anhydrase IX (CAIX) plays a crucial role in cancer progression. CAIX is a 459-amino acid transmembrane protein consisting of five components: an extracellular signal peptide, a mucin domain, a catalytic domain, a transmembrane segment, and a short cytoplasmic peptide. Recent studies have shown that CAIX is a downstream transcriptional protein of the hypoxia-inducible factor-1α (HIF-1α) gene. It is specifically overexpressed on the cell surface of many hypoxic malignancies, including breast, lung, ovarian, head and neck, bladder, colon, cervical, and renal cancers, while its expression in normal tissues is very limited. Therefore, CAIX has the potential to become a diagnostic and therapeutic target for cancer. Therefore, the construction of a molecular probe dually targeting CAIX and FAP has significant research significance and clinical application value for the sensitive early diagnosis and detection of primary and metastatic lesions in various tumors. Summary of the Invention

[0004] The present invention aims to improve the early diagnostic accuracy and sensitivity of FAP probes by introducing CAIX, another overexpressed tumor receptor, as a second targeting moiety, leveraging the overexpression of CAIX receptors in the tumor microenvironment. This approach overcomes the low diagnostic accuracy and sensitivity of existing FAP-04-type broad-spectrum tumor imaging agents. To this end, the present invention provides a compound or salt thereof, as shown in Formula I, that dually targets CAIX and FAP.

[0005] A second object of the present invention is to provide a radionuclide label of a compound or a salt thereof that targets both CAIX and FAP, the structure of which is shown in Formula II.

[0006] A third object of the present invention is to provide a method for preparing the compound or its salt that targets both CAIX and FAP as shown in Formula I.

[0007] A fourth object of the present invention is to provide a method for preparing a radionuclide-labeled compound or a salt thereof targeting both CAIX and FAP as shown in Formula II.

[0008] A fifth object of the present invention is to provide a radionuclide labeling application of a compound or salt thereof targeting both CAIX and FAP as shown in Formula I, or a compound or salt thereof targeting both CAIX and FAP as shown in Formula II.

[0009] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0010] The present invention discloses a compound or a salt thereof targeting CAIX and FAP, the structure of which is shown in Formula I:

[0011]

[0012] The radionuclide label of the compound or salt thereof targeting CAIX and FAP disclosed in the present invention has a structure as shown in Formula II.

[0013]

[0014] Where A is a radionuclide.

[0015] In some embodiments of the present invention, the radionuclide comprises 68 Ga, 177 Lu, 99m Tc、、 111 In, 67 Ga, 86 Y. 90 Y. 161 Tb, 186 Re、188 Re、 64 Cu, 67 Cu, 211 At 225 Ac, 18 F. 123 I. 124 I. 125 At least one of I;

[0016] Preferably, 68 Ga, 177 Lu, 99m Tc, 111I n. 64 Cu, 18 F or 225 At least one of Ac;

[0017] More preferably 68 Ga, 177 Lu or 225 At least one of Ac.

[0018] In some embodiments of the present invention, the radionuclide is 68 The structure of the Ga, radionuclide label is shown in Formula III:

[0019]

[0020] In some embodiments of the present invention, the radionuclide is 177 The structure of Lu, a radionuclide label, is shown in Formula IV:

[0021]

[0022] The present invention discloses a method for preparing a compound targeting CAIX and FAP, comprising the following steps: reacting compound 3 (compd3) with compound 10 (compd10) to generate compound 11 (compd11); and then reacting compound 11 (compd11) with compound 12 (compd12) to generate a compound of formula I. The synthetic route is as follows:

[0023]

[0024] The method for preparing a radionuclide label of a compound targeting CAIX and FAP disclosed in the present invention comprises the following steps: reacting a compound of formula I with a radionuclide salt to generate a radionuclide label represented by formula II.

[0025] The present invention discloses a pharmaceutical composition comprising the aforementioned compound targeting CAIX and FAP or a salt thereof; or a radionuclide label of the aforementioned compound targeting CAIX and FAP or a salt thereof.

[0026] Use of the compound or salt thereof targeting CAIX and FAP disclosed herein, or a radionuclide label of the compound or salt thereof targeting CAIX and FAP, in the preparation of a product for detecting and / or detecting cells and / or tissues expressing FAP receptors and CAIX receptors;

[0027] Preferably, the product comprises a diagnostic tracer and / or a therapeutic agent;

[0028] More preferably, the diagnostic tracer is used for positron emission tomography, computed tomography, positron emission tomography, single photon emission tomography or single electron emission computed tomography.

[0029] The present invention discloses the use of the above-mentioned compound targeting CAIX and FAP or its salt, or the radionuclide label of the above-mentioned compound targeting CAIX and FAP or its salt, in the preparation of a product for diagnosing and / or treating prostate cancer, pre-metastatic prostate cancer, colon cancer, breast cancer, kidney cancer or bladder cancer.

[0030] Compared with the prior art, the present invention has the following beneficial effects:

[0031] The present invention is scientifically designed and ingeniously conceived. The compound of the present invention can simultaneously target FAP receptors and CAIX receptors, overcoming the problems of low diagnostic accuracy and low sensitivity of tumor imaging agents in the prior art. Experimental results show that the radionuclide label of the present invention is relatively 68 Ga-FAP-04 has better uptake at the tumor site, higher sensitivity, longer uptake time at the tumor site, is more conducive to tumor diagnosis and treatment, and is cleared quickly by the kidneys.

[0032] The compound of the present invention or its radionuclide marker is used for diagnosing and / or treating tumors expressing FAP receptors and CAIX receptors, and has advantages such as high affinity, high T / NT value and rapid renal clearance.

[0033] The Chinese name corresponding to the English abbreviation of the present invention is:

[0034] Sodium ascorbate: Ascorbic acid

[0035] DMF: N,N-dimethylformamide

[0036] HATU: 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate

[0037] DIEA: N,N-diisopropylethylamine

[0038] TFA: trifluoroacetic acid

[0039] Piperidine: Piperidine

[0040] EDCI: carbodiimide

[0041] HOOBt: 3-Hydroxy-1,2,3-benzotriazin-4(3H)-one

[0042] NMM: N-methylmorpholine BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Figure 1 This is a synthetic route for the compound DOTA-CAIX-FAP of Example 1 of the present invention.

[0044] Figure 2 This is the mass spectrum of DOTA-CAIX-FAP.

[0045] Figure 3 This is the UV spectrum of DOTA-CAIX-FAP.

[0046] Figure 4 for 68 Radio-HPLC spectrum of Ga-DOTA-CAIX-FAP.

[0047] Figure 5 for 177 Radio-TLC spectrum of Lu-DOTA-CAIX-FAP.

[0048] Figure 6 for 68 Radio-HPLC spectrum of Ga-FAP04.

[0049] Figure 7 for 68 PET / CT images of Ga-CAIX-FAP on U87MG model.

[0050] Figure 8 for 68 PET / CT images of Ga-FAPI-4 on the U87MG model.

[0051] Figure 9 for 177 SPETCT / CT images of Lu-CAIX-FAP on U87MG model.

[0052] Figure 10 for 68 Figure 3 shows the in vitro stability of Ga-CAIX-FAP in PBS and 10% FBS.

[0053] Figure 11 This is a diagram showing the cell uptake experimental results of Experimental Example 4. DETAILED DESCRIPTION

[0054] In order to make the purpose, technical scheme and advantages of the embodiments of the present invention clearer, the technical scheme in the embodiments of the present invention will be clearly and completely described below in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Those who do not indicate specific conditions in the examples are carried out according to normal conditions or the conditions recommended by the manufacturer. Those whose reagents or instruments are not indicated by the manufacturer are all conventional products that can be purchased commercially.

[0055] Example 1

[0056] This embodiment discloses the synthesis of the compound DOTA-CAIX-FAP of formula I of the present invention. The synthesis route is shown in the attached Figure 1 shown.

[0057] The specific steps are as follows:

[0058] Compd 1 (1 eq) and Compd 2 (2 eq) were dissolved in 5 ml of H2O / EtOH (V:V = 2:3) solution. CuSO45H2O (0.2 eq) and sodium ascorbate (0.4 eq) were added under nitrogen protection. The reaction was allowed to react at room temperature for 3 hours. The reaction was monitored to be complete by LC-MS. The product was concentrated and purified by reverse phase preparative liquid chromatography to obtain Compd 3 (yield: 90%).

[0059] 2. Compd 5 (1.2 eq) was dissolved in 10 ml of DMF, and HATU (1 eq) and DIEA (3 eq) were added. The mixture was stirred for 5 minutes, and then Compd 4 (4 eq) was added. The reaction was allowed to proceed overnight at room temperature. The reaction was complete as monitored by LC-MS. The product was concentrated, and 5 mL of TFA was added. The reaction was allowed to proceed at room temperature for 5 minutes. 50 mL of ether was added, the product was centrifuged, and the mixture was drained. The product was purified by reverse phase preparative liquid chromatography to obtain Compd 6 (yield: 62%).

[0060] 3. Compd 7 (1 eq) was dissolved in 10 ml of DMF, and HATU (1 eq) and DIEA (1 eq) were added. The reaction was allowed to proceed for 5 minutes, and then Compd 6 (1 eq) was added. The reaction was allowed to proceed at room temperature for 2 hours. The reaction was complete after monitoring by LC-MS. The product was concentrated, and 5 mL of 20% piperidine / DMF was added. The reaction was allowed to proceed at room temperature for 5 minutes. Then, 50 mL of ether was added. The product was centrifuged and dried. The product was purified by reverse phase preparative liquid chromatography to obtain Compd 8 (Yield: 60%).

[0061] 4. Compd 9 (1 eq) was dissolved in 10 ml of DCM. EDCI (1 eq) and HOOBt (1 eq) were added at 0°C and reacted for 10 minutes. Compd 8 (1 eq) and NMM (3 eq) were then added. The reaction was transferred to room temperature for 2 hours. The reaction was complete after monitoring by LC-MS. The product was concentrated, 5 mL of 20% piperidine / DMF was added, and the reaction was continued at room temperature for 5 minutes. 50 mL of ether was added, the product was centrifuged, and dried. Compd 10 was purified by reverse phase preparative liquid chromatography (yield: 29%).

[0062] 5. Compd 3 (1 eq) was dissolved in 5 ml of DCM. EDCI (1 eq) and HOOBt (1 eq) were added at 0°C and reacted for 10 minutes. Compd 10 (1 eq) and NMM (3 eq) were then added. The reaction was transferred to room temperature and allowed to react overnight. The reaction was complete after monitoring by LC-MS. The product was concentrated and 5 ml of TFA solution was added. The reaction was allowed to react at room temperature for 30 minutes. 50 mL of ether was then added. The product was centrifuged and drained. The product was purified by reverse phase preparative liquid chromatography to obtain Compd 11 (yield: 46%).

[0063] 6. Compd 11 (1 eq) and Cmpd 12 (1.2 eq) were dissolved in 5 ml of DMF, and DIEA (3 eq) was added; the mixture was reacted at room temperature for 2 hours, concentrated, and purified by reverse phase preparative liquid chromatography to obtain the compound of formula I, DOTA-CAIX-FAP (yield: 57%).

[0064] Its mass spectrum is as follows Figure 2 As shown, HPLC diagram is shown Figure 3 shown.

[0065] Example 2

[0066] This embodiment discloses a radionuclide label of a compound of formula I. 68 The preparation method of Ga-DOTA-CAIX-FAP is as follows:

[0067] Using DOTA-CAIX-FAP compound as a precursor, DOTA-CAIX-FAP was prepared into a 1 μg / μl precursor aqueous solution for standby use.

[0068] Take 30 μl of the above precursor solution and add it to 37 MBq of 68 GaCl3 solution, and adjust the pH to 4-5 with 0.25M sodium acetate buffer, react at 90℃ for 15min. Add 5ml of saline to the reaction solution and pass it through a C18 light column. Use 20ml of saline to wash the residual 68 The product in the C18 column was eluted with 1 ml of 50% ethanol solution, passed through a 0.22 μm sterile filter membrane, and finally diluted to below 10% ethanol concentration.68 The radiochemical purity of Ga-DOTA-CAIX-FAP is >98%, as Figure 4 shown.

[0069] Example 3

[0070] This embodiment discloses 177 The preparation method of Lu-DOTA-CAIX-FAP is as follows:

[0071] Using the DOTA-CAIX-FAP compound as a precursor, DOTA-CAIX-FAP was prepared into a 1 μg / μl aqueous solution for later use.

[0072] Take 30 μl of the above precursor solution and add it to 370 MBq of 177 LuCl3 solution, and adjust the pH to 4-5 with 0.25M sodium acetate buffer, react at 90℃ for 15min. Add 5ml of saline to the reaction solution and pass it through C18 light column, and rinse the residual on the C18 column with 20ml of saline. 177 LuCl3. Elute the product in the C18 column with 2 ml of 50% ethanol solution, pass through a 0.22 μm sterile filter membrane, and finally dilute the ethanol concentration to below 10%. 177 The radiochemical purity of Lu-DOTA-CAIX-FAP is >98%, as Figure 5 shown.

[0073] Comparative Example 1

[0074] This comparative example discloses 68 Preparation of Ga-FAPI-4: The FAPI-4 in this comparative example was provided by Ganzhou Tanzhen Biopharmaceutical Co., Ltd.

[0075] Using FAPI-4 compound as a precursor, FAPI-4 was prepared into a 1 μg / μl precursor aqueous solution for standby use.

[0076] Take 50 μl of the above precursor solution and add it to 370 MBq of 68 GaCl3 solution, and adjust the pH to 4-5 with 0.25M sodium acetate buffer, react at 90℃ for 15min. Add 5ml of saline to the reaction solution and pass it through a C18 light column. Use 20ml of saline to wash the residual 68 The product in the C18 column was eluted with 1 ml of 50% ethanol solution, passed through a 0.22 μm sterile filter membrane, and finally diluted to below 10% ethanol concentration. 68 The radiochemical purity of Ga-FAPI-4 is >98%, as Figure 6 shown.

[0077] Test Example 1

[0078] This test example discloses 68 Ga-DOTA-CAIX-FAP, 68 Ga-FAPI-4 and 177 PET / CT imaging experiment of Lu-DOTA-CAIX-FAP.

[0079] Establishment of U87MG animal model: U87MG cells expressing FAP were cultured in DMEM medium containing 10% FBS at 37°C, 5% CO2, and saturated humidity. After the cells grew to 70-80%, they were trypsinized and centrifuged before inoculation. BALB / c-nu nude mice were anesthetized and inoculated subcutaneously in their axilla. The number of cells inoculated per BALB / c-nu nude mouse was 5*10 6 cell / piece / 0.1ml. Wait until the tumor size grows to 400-500mm 3 It can be used for imaging experiments.

[0080] In this test example 68 Ga-DOTA-CAIX-FAP was prepared according to the method of Example 1; 177 Lu-DOTA-CAIX-FAP was prepared according to the method of Example 2; 68 Ga-FAPI-4 was prepared according to the method of Comparative Example 1. 68 Ga-DOTA-CAIX-FAP was injected into U87MG tumor-bearing mice with high FAP expression via the tail vein. PET / CT imaging was performed 0.5 h, 1 h, and 1.5 h after injection. The results were as follows: Figure 7 shown.

[0081] Take 1.5mci 177 Lu-DOTA-CAIX-FAP was injected into U87MG tumor-bearing mice with high FAP expression via the tail vein. SPETCT / CT imaging was performed 4h, 24h, 48h, 96h, and 166h after injection. The results are as follows: Figure 9 shown.

[0082] Take 100μci 68 Ga-FAPI-4 was injected into U87MG tumor-bearing mice with high FAP expression via the tail vein. PET / CT imaging was performed 0.5 h, 1 h, and 1.5 h after injection. The results were as follows: Figure 8 shown.

[0083] result:

[0084] (1) From Figure 6 It can be seen that the radionuclide label of the compound of formula I of the present invention 68Ga-DOTA-CAIX-FAP was specifically taken up in the U87MG tumor site, and had low uptake in other organs.

[0085] (2) From Figure 7 It can be seen that the comparative example 1 68 The uptake of Ga-FAPI-4 in the U87MG tumor model was low at 0.5h, 1h, and 1.5h.

[0086] (3) From Figure 8 It can be seen that the radionuclide label of the compound of formula I of the present invention 177 Lu-DOTA-CAIX-FAP was specifically taken up in the U87MG tumor site and still had a high uptake at 166 h.

[0087] The above results show that the radionuclide label of the present invention is 68 Ga-FAPI-4 has better uptake at the tumor site, higher sensitivity, longer uptake time at the tumor site, is more conducive to tumor diagnosis and treatment, and is cleared quickly by the kidneys.

[0088] Test Example 2

[0089] This test example discloses 68 Ga-DOTA-CAIX-FAP and 177 In vitro stability experimental data of Lu-DOTA-CAIX-FAP.

[0090] In this test example 68 Ga-DOTA-CAIX-FAP was prepared according to the method of Example 1; 177 Lu-DOTA-CAIX-FAP was prepared according to the method of Example 2.

[0091] The cells were analyzed by incubation in saline or 10% bovine serum albumin for 15, 30, 60, and 120 minutes in vitro. 68 The in vitro stability of Ga-DOTA-CAIX-FAP was analyzed by radio-HPLC. The radiochemical purity was greater than 95% within 2 hours after incubation with normal saline or 10% bovine serum albumin. Figure 9 shown.

[0092] Take 20 μL and 100 μci of marker in parallel 68Ga-DOTA-CAIX-FAP was dissolved in three 180 μL tubes of PBS or 10% bovine serum albumin (FBS) and incubated at 37°C for 15 min, 30 min, 60 min, and 120 min. Samples were taken at each time point and the radiochemical purity was analyzed by radio-HPLC to investigate its in vitro stability.

[0093] Determined by the same method 177 The in vitro stability of Lu-DOTA-CAIX-FAP in PBS and 10% bovine serum albumin. 68 Ga-DOTA-CAIX-FAP and 177 Lu-DOTA-CAIX-FAP has good in vitro stability, and the radiochemical purity is greater than 95% within 2 hours after incubation in PBS or 10% bovine serum albumin. Figure 10 shown.

[0094] Test Example 3

[0095] This test example discloses 68 The lipid-water partition coefficient of Ga-DOTA-CAIX-FAP was investigated. 68 Ga-DOTA-CAIX-FAP was prepared according to the method of Example 1.

[0096] 68 The lipid-water partition coefficient of Ga-DOTA-CAIX-FAP was tested by the following method: 68 Ga-DOTA-CAIX-FAP (50 μl, 0.37 Mbq) was added to a mixed solution of n-octanol and PBS, and the volume ratio of the organic phase to the aqueous phase was finally maintained at 1:1 (n=5). The mixture was vortexed for 3 minutes and centrifuged at 3000× rpm for 5 minutes. Then, 3 samples (50 μL) were taken from each phase and the radioactive counts were determined using a γ counter (HIDEX,). The distribution coefficient was calculated as the counts in n-octanol divided by the counts in phosphate-buffered saline. 68 The lipid-water partition coefficient of Ga-DOTA-CAIX-FAP is logD7.4=-3.89, indicating that 68 Ga-DOTA-CAIX-FAP has excellent hydrophilicity.

[0097] Test Example 4

[0098] This test example discloses 68 Ga-DOTA-CAIX-FAP cell uptake assay, in this test example 68 Ga-DOTA-CAIX-FAP was prepared according to the method of Example 1.

[0099] U87MG cells expressing FAP were cultured in DMEM medium containing 10% FBS. After the cells grew to 70-80% of the total mass, they were digested with trypsin and seeded into 24-well plates (approximately 1.5*10 5 Cells / well) were cultured overnight at 37°C, 5% CO2. The next day, cells were starved with pure DMEM medium, and then approximately 50 μl / 1 μCi / well of radiolabeled product was added. The cells were incubated in an incubator for 15 min, 30 min, 60 min, and 120 min. The cell uptake value at each time point was measured using a gamma counter (n ≥ 3). The data obtained are shown in Figure 2. Figure 11 .

[0100] Depend on Figure 11 It can be seen that 68 Ga-DOTA-CAIX-FAP showed a high uptake in FAP-positive U87MG cells (>15% ID / 10 6 Cell), within 15min, 30min, 60min, and 120min, the cells 68 The uptake of Ga-DOTA-CAIX-FAP did not decrease, but showed a slow upward trend, proving that 68 Ga-DOTA-CAIX-FAP binds stably to the FAP target and is not prone to off-target effects.

[0101] The embodiments described above are only some of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

Claims

1. A compound targeting CAIX and FAP or a salt thereof, characterized in that: Its structure is shown in Formula I: Formula I.

2. A radionuclide label of a compound targeting CAIX and FAP or a salt thereof according to claim 1, characterized in that: Its structure is shown in Formula II, Formula II Where A is 68 Ga or 177 Lu.

3. The radionuclide label of a compound targeting CAIX and FAP or a salt thereof according to claim 2, characterized in that: Radionuclides are 68 The structure of the Ga, radionuclide label is shown in Formula III: Formula III.

4. The radionuclide label of a compound targeting CAIX and FAP or a salt thereof according to claim 2, characterized in that: Radionuclides are 177 The structure of Lu, a radionuclide label, is shown in Formula IV: Formula IV.

5. The method for preparing a compound targeting CAIX and FAP according to claim 1, characterized in that: The method comprises the following steps: compound 3 reacts with compound 10 to generate compound 11; compound 11 then reacts with compound 12 to generate a compound of formula I. The synthetic route is as follows: 。 6. The method for preparing a radionuclide labeled compound targeting CAIX and FAP or a salt thereof according to claim 2, characterized in that: The method comprises the following steps: reacting a compound of formula I with a radioactive nuclide salt to generate a radioactive nuclide label represented by formula II; the compound of formula I has the following structural formula: Formula I.

7. A pharmaceutical composition, characterized in that A radionuclide label comprising the compound targeting CAIX and FAP or a salt thereof according to any one of claims 2 to 4.

8. Use of the radionuclide label of the compound targeting CAIX and FAP or a salt thereof according to any one of claims 2 to 4 in the preparation of a product for detecting cells and / or tissues expressing FAP receptors and CAIX receptors.

9. The use according to claim 8, characterized in that The products include diagnostic tracers.

10. The use according to claim 9, characterized in that The diagnostic tracer is used for positron emission tomography, electronic computed tomography, positron emission tomography, single photon emission tomography or single electron emission computed tomography.

11. Use of the radionuclide label of the compound targeting CAIX and FAP or a salt thereof according to any one of claims 2 to 4 in the preparation of a product for diagnosing prostate cancer, colon cancer, breast cancer, kidney cancer or bladder cancer.

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