A radioiodinated FAP-2286 precursor for tumors and preparation method and application

Abstract

The application relates to the technical field of tumor imaging agents, in particular to IPC C07K5, and more particularly to a radioiodine-labeled FAP-2286 precursor applied to tumors, a preparation method and application. A tyrosine structure is connected to the structure of FAP-2286, so that a FAP-2286 precursor capable of being connected with a radioiodine nuclide is obtained. The FAP-2286 precursor in the application increases a radioiodine modification site, and the detection accuracy is improved.

Description

Technical Field

[0001] This invention relates to the field of tumor imaging agents, particularly to IPC C07K5, and more specifically to a radioactive iodine-labeled FAP-2286 precursor for use in tumors, its preparation method, and its application. Background Technology

[0002] FAP (fibroblast activator protein) is a single-channel type II transmembrane glycoprotein with a large extracellular domain composed of α / β-hydrolases and a β-propeller. It is highly expressed in tumor-associated fibroblasts in various epithelial cancer microenvironments, influencing tumor growth, metastasis, and invasion. FAP-2286, as an FAP inhibitor, is a macrocyclic compound of FAP-binding peptide conjugated to the radionuclide chelator DOTA.

[0003] Existing patent CN202210249841.0 indicates that commonly used... 18 F-labeled FAPI-04 imaging agents possess high tumor / target organ uptake ratios and rapid clearance. However, in pancreatic tumors, uptake is relatively unstable and varied, and a small percentage of patients experience physiological uptake by the biliary system, leading to misjudgment. Furthermore, some gallium-labeled imaging agents have short half-lives, making them unsuitable for long-distance transport. Some FAP-related tumors also exhibit low uptake rates of the imaging agents. Therefore, there is a need to develop a radioiodine-labeled FAP-2286 precursor for tumor imaging with high uptake rates, high accuracy, and high specificity. Summary of the Invention

[0004] To address the problems in the prior art, the first aspect of the present invention provides a radiolabeled iodine precursor for tumors, the structural formula of which is shown in formula (1):

[0005]

[0006] Preferably, the R group is any one of formula (2), formula (3), and formula (4);

[0007]

[0008] More preferably, the R group is of formula (2).

[0009] In this invention, a novel FAP-2286 precursor was obtained by attaching a tyrosine residue to the structure of FAP-2286. This precursor can be linked to radioactive iodine or tumor drugs. By binding to radioactive iodine or tumor drugs, the location and size of tumors can be observed, or targeted drug administration can be performed on tumors, achieving an integrated diagnostic and therapeutic effect. The inventors have creatively discovered that FAP-2286, as a compound capable of targeting and activating fibroblasts, exhibits good binding activity and inhibitory effects. It is typically labeled with gallium, but can only be labeled with gallium, which has certain limitations. (Nucleotide) 68 Ga is mainly produced using a 68Ge / 68Ga generator, a process that is complex and yields low output per batch. 68 Ga-FAPI drugs can only meet the needs of a small number of patients; furthermore... 68 Gallium (Ga) has a short half-life of only about 68 minutes, leading to rapid clearance from the body. This invention adds a tyrosine residue to FAP-2286, enabling the attachment of radioactive iodine to the FAP-2286 precursor. This maintains the original compound's function while adding a radioactive iodine modification site, allowing it to bind to different isotopes of iodine. When bound to radioactive iodine, it can reveal the size and location of tumors. Furthermore, the long half-life of radioactive iodine results in higher tumor uptake and longer retention time, leading to stronger tumor-killing efficacy. Adding a tyrosine group to FAP-2286 yields the FAP-2286 precursor, which can simultaneously label both radioactive gallium and radioactive iodine. This allows for the introduction of two nuclides into the same molecule, increasing the detectable methods. Gallium can be detected using PET, and iodine can be detected using ECT, enabling dual-nucleoside detection and improving accuracy.

[0010] A second aspect of the present invention provides a method for preparing a radiolabeled FAP-2286 precursor for use in tumors, comprising the following steps:

[0011] S1: Resin swelling: Place 2-Chlorotrityl Chloride Resin into a reaction tube, add DMF 12-18 mL / g, and shake for 55-65 min;

[0012] S2: Connects to the first amino acid Fmoc-Cys(Mtt)-OH;

[0013] S3: Deprotection, detection, and resin rinsing;

[0014] S4: Condensation, inspection, and resin rinsing;

[0015] S5: Repeat S3 to S4, connecting amino acids sequentially;

[0016] S6: Rinse resin, remove protection, rinse resin;

[0017] S7: Remove solvent and inoculate with 1,3,5-Tris(bromomethyl)benzene;

[0018] S8: Rinse the resin to obtain a reaction tube containing a Tris(bromomethyl)benzene peptide chain;

[0019] S9: Prepare another reaction tube, add 2-Chlorotrityl Chloride Resin, and inoculate with amino acids;

[0020] S10: Repeat step S3, then add DOTA-tris(tBu ester) to react;

[0021] S11: DOTA-tris(tBu ester)-Y(tbu) polypeptide was obtained by cleavage from resin;

[0022] S12: Dissolve the DOTA-tris(tBu ester)-Y(tbu) polypeptide in DCM, add NH2CH2CH2SH, perform PyBop reaction, and then remove the solvent;

[0023] S13: Dissolve the peptide obtained in S12 and add it to a reaction tube containing a Tris(bromomethyl)benzene peptide chain for reaction.

[0024] S14: Rinse the resin, prepare the cutting fluid to cut the peptide chain, and blow dry and wash.

[0025] S15: Purification and preparation.

[0026] Preferably, the specific steps of S2 are as follows: filter out the solvent in the reaction tube of S1 by sand core filtration, add 3 parts of excess Fmoc-Cys(Mtt)-OH amino acid (the first amino acid at the C-terminus), add 10 times the excess DIEA, and finally add DMF to dissolve. Shake for 25-35 min, seal with methanol, and let sit for 25-35 min.

[0027] Preferably, the deprotection process in S3 is as follows: remove DMF, add 12-18 mL / g of 20% piperidine DMF solution, react for 4-6 min, remove the 20% piperidine DMF solution and add another 20% piperidine DMF solution (15 mL / g), react for 10-20 min.

[0028] Preferably, the mass ratio of piperidine to DMF is 1:4.

[0029] Preferably, the detection process in S3 is as follows: remove the piperidine DMF solution, take the resin, wash it with ethanol 3 to 4 times, add one drop each of ninhydrin, KCN, and phenol solution, heat at 105℃ to 110℃ for 5 to 7 minutes, and a deep blue color indicates a positive reaction.

[0030] Preferably, the resin rinsing process in S3, S4, S6, and S8 is as follows: rinse twice with DMF (10 mL / g), rinse twice with methanol (10 mL / g), and rinse twice with DMF (10 mL / g) in sequence.

[0031] Preferably, the condensation process in S4 is as follows: add 3 times molar excess of Fmoc to protect amino acids, 3 times molar excess of HBTU, then add 10 times molar excess of DIEA, and finally add DMF to dissolve, and shake for 45-50 minutes.

[0032] Preferably, the Fmoc protected amino acid is Fmoc-Pro-OH.

[0033] Preferably, the detection process in S4 involves removing the DMF solution, taking the resin, washing it 3-4 times with ethanol, adding one drop each of ninhydrin, pyridine, and phenol solution, heating it at 105℃-110℃ for 5-7 minutes, and a deep blue color indicating a positive reaction.

[0034] Preferably, the amino acids sequentially linked in S5 are Fmoc-Pro-OH, Fmoc-Thr(tbu)-OH, Fmoc-Gln(Trt)-OH, and Fmoc-Phe-OH, respectively.

[0035] Preferably, in step S6, deprotection is performed by removing the solution, adding 2% TFA / DMF solution (10 mL / g), and reacting for 2–2.5 h to remove the cysteine ​​protecting group Mtt.

[0036] Preferably, the mass ratio of TFA to DMF is 1:49.

[0037] Preferably, the process of adding 1,3,5-Tris(bromomethyl)benzene is as follows: add 3 times the molar excess of 1,3,5-Tris(bromomethyl)benzene, add DMF, add triethylamine as an acid-binding agent, ensure that the entire system is anhydrous, and carry out the process at 80-85°C.

[0038] Preferably, the specific process of adding amino acids is as follows: the solvent is removed by filtration through a sand core, 3 times the molar excess of Fmoc-amino acid-OH is added, then 10 times the molar excess of DIEA is added, and finally DMF is added to dissolve. The mixture is shaken for 25-35 minutes, and the head is sealed with methanol for 25-35 minutes.

[0039] Preferably, the amino acid is Fmoc-Tyr(tbu)-OH, Fmoc-Trp(tbu)-OH, or Fmoc-His(tbu)-OH.

[0040] Preferably, the process of adding DOTA-tris(tBu ester) is as follows: add 3 times molar excess of DOTA-tris(tBu ester), 3 times molar excess of HBTU, then add 10 times molar excess of DIEA, and finally add DMF to dissolve, and shake for 45-50 min.

[0041] Preferably, the cutting fluid used in S11 is a mixed solution of trifluoroethanol and DCM, with a dosage of 10 mL / g and a cutting time of 120–130 min;

[0042] Preferably, the mass ratio of trifluoroethanol to DCM is 3:7.

[0043] Preferably, the specific process of adding NH2CH2CH2SH, reacting with PyBop, and then removing the solvent is as follows: add 3 times the molar excess of NH2CH2CH2SH, 2 times the molar excess of PyBop, and 10 times the excess of DIEA, reflux at 45-50°C, react for 2-3 hours, and then remove the solvent by rotary evaporation.

[0044] Preferably, the solvent dissolved in S13 is DMF, and the reaction conditions are: using DMF as the reaction solvent, triethylamine as the acid-binding agent, ensuring that the entire system is anhydrous, and carrying out the reaction at 80-90°C.

[0045] Preferably, the specific steps for rinsing the resin in S14 are: DMF (10 mL / g) twice, DCM (10 mL / g) three times, methanol (10 mL / g) four times, and then drying for 10 min.

[0046] Preferably, the raw materials of the cutting fluid in S14, by mass percentage, are 94.5% TFA; 2.5% water; 2.5% EDT; and 1% TIS.

[0047] Preferably, the cutting time in S14 is 180-200 minutes.

[0048] Preferably, the drying and washing process in S14 involves drying the lysis buffer as much as possible with nitrogen gas, adding diethyl ether to precipitate the lysate, centrifuging to remove the supernatant, washing the precipitate with diethyl ether 6-8 times, and then evaporating it at room temperature.

[0049] Preferably, the specific process of purification and preparation is as follows: dissolve the crude product with H2O and ACN solution, find the target peak of the target peptide chain with HPLC analysis instrument, and record the corresponding peak time; collect the target peak solution with C18 reversed-phase chromatography preparation system, freeze-dry, and obtain FAP-2286 precursor.

[0050] A third aspect of the present invention provides an application of a radiolabeled FAP-2286 precursor for use in tumors, for the preparation of antitumor drugs or tumor imaging agents.

[0051] Preferably, the tumor is a solid tumor.

[0052] Preferably, the solid tumor is a breast tumor, pancreatic tumor, liver tumor, or gastric tumor; more preferably, it is a breast tumor.

[0053] Preferably, the method of application is to combine the FAP-2286 precursor with radioactive iodine.

[0054] Beneficial effects

[0055] In this invention, a new FAP-2286 precursor is obtained by attaching a tyrosine structure to the structure of FAP-2286. This precursor can be linked to radioactive iodine or tumor drugs. By combining with radioactive iodine or tumor drugs, the location and size of the tumor can be observed, or targeted drug administration can be performed on the tumor, achieving the effect of integrated diagnosis and treatment. Attached Figure Description

[0056] Figure 1 The MS molecular weight analysis spectrum of the FAP-2286 precursor in Example 1;

[0057] Figure 2 This is an HPLC purity analysis chromatogram of the FAP-2286 precursor in Example 1.

[0058] Figure 3 This image shows the uptake of FAP-2286 precursor by mouse tumors after binding with radioactive iodine in Example 1. The area circled in white in the image represents... 131 3D map of the in vivo distribution of I-Tyr-FAP-2286 in mice bearing breast cancer (4T1 cells) 2 hours after tail vein injection, with an uptake rate of 3.11 ± 0.70% ID.

[0059] Figure 4 To investigate the effects of tail vein injection of iodine-labeled FAP-2286 precursor into mice bearing breast cancer (4T1 cells), the uptake of iodine-labeled FAP-2286 by the mice was compared with that of FAP-2286 two hours after injection. 68 A graph showing the uptake of Ga. Detailed Implementation

[0060] Example 1

[0061] This embodiment provides a radiolabeled FAP-2286 precursor for use in tumors, characterized by the following structural formula:

[0062]

[0063] The second aspect of this embodiment provides a method for preparing a radiolabeled FAP-2286 precursor for use in tumors, comprising the following steps:

[0064] S1: Resin swelling: Place 10g of 2-Chlorotrityl Chloride resin with a degree of substitution of 1.1mmol / g into a reaction tube, add DMF (15mL / g), and shake for 60min;

[0065] S2: Filter the solvent through a sand core to remove the solvent, add 3.5 molar amounts of Fmoc-Cys(Mtt)-OH amino acid (the first amino acid at the C-terminus), then add 12 molar amounts of DIEA (based on the molar amount of Fmoc-Cys(Mtt)-OH, with subsequent multiples based on this Fmoc-Cys(Mtt)-OH), finally add the same volume of DMF as the resin to dissolve, shake for 30 min; add half the volume of DMF from S2 to cap the reaction with methanol, and react for 30 min.

[0066] S3: Remove DMF, add 20% piperidine DMF solution (15 mL / g) (piperidine to DMF mass ratio is 1:4), react for 5 min, remove the 20% piperidine DMF solution and add another 20% piperidine DMF solution (15 mL / g), react for 15 min; remove the piperidine DMF solution, take 15 resin grains, wash three times with ethanol, add one drop each of ninhydrin, KCN, and phenol solution, heat at 110℃ for 5 min, a deep blue color indicates a positive reaction; wash twice with DMF (10 mL / g), twice with methanol (10 mL / g), and twice with DMF (10 mL / g) in sequence;

[0067] S4: Add 3.5 molar Fmoc-Pro-OH, 3.5 molar HBTU, then add 12 molar DIEA, and finally add DMF to dissolve. Shake for 45 min. Take 15 resin grains, wash three times with ethanol, add one drop each of ninhydrin, pyridine, and phenol solution, heat at 110℃ for 5 min, and a deep blue color indicates a positive reaction. Rinse once with DMF (10 mL / g), twice with methanol (10 mL / g), and twice with DMF (10 mL / g).

[0068] S5: Repeat S3 to S4, connecting Fmoc-Pro-OH, Fmoc-Thr(tbu)-OH, Fmoc-Gln(Trt)-OH and Fmoc-Phe-OH in sequence respectively;

[0069] S6: Rinse twice with DMF (10 mL / g), twice with methanol (10 mL / g), and twice with DMF (10 mL / g) in sequence; remove the solution, add 2% TFA / DMF solution (10 mL / g), where the mass ratio of TFA to DMF is 1:49, react for 2 h to remove the protecting group Mtt ​​of cysteine; rinse twice with DMF (10 mL / g), twice with methanol (10 mL / g), and twice with DMF (10 mL / g) in sequence.

[0070] S7: Remove the solvent, add 3.5 moles of 1,3,5-Tris(bromomethyl)benzene, add DMF (10 mL / g), and add triethylamine as an acid-binding agent. The mass ratio of triethylamine to triethylamine in S7 is 1:49. Ensure that the entire system is anhydrous and carry out the reaction at 80°C.

[0071] S8: Wash twice with DMF (10 mL / g), twice with methanol (10 mL / g), and twice with DMF (10 mL / g) to obtain a reaction tube containing a Tris (bromomethyl)benzene peptide chain; the units of S1 to S8 are all in the form of 2-Chlorotrityl Chloride Resin in S1;

[0072] S9: Prepare another reaction tube, put 10g of 2-Chlorotrityl Chloride Resin into the reaction tube, add DMF (15mL / g), and shake for 60min; filter the solvent through a stencil, add 3.5 molars of Fmoc-Tyr(tbu)-OH, then add 12 molars of DIEA, and finally add DMF to dissolve, shake for 30min; seal with methanol, and shake for 30min;

[0073] S10: Repeat step S3, then add 3.5 moles of DOTA-tris (tBu ester), 3.5 moles of HBTU, then add 12 moles of DIEA, and finally add DMF to dissolve. Shake for 45 min.

[0074] S11: Prepare the cutting solution (10 mL / g), which is a solution of trifluoroethanol and DCM mixed in a mass ratio of 3:7; cut with the cutting solution, and remove the solvent by rotary evaporation to obtain the DOTA-tris(tBu ester)-Y(tbu) polypeptide.

[0075] S12: Dissolve the DOTA-tris(tBu ester)-Y(tbu) polypeptide in DCM, add 3.5 molar NH2CH2CH2SH (2-aminoethanethiol), two times excess PyBop, 12 times DIEA, reflux at 45℃, react for 2 h, and remove the solvent by rotary evaporation.

[0076] S13: Dissolve the obtained protected peptide DOTA-tris(tBu ester)-Y(tbu)-NHCH2CH2SH in DMF, then add it to a reaction tube containing a Tris(bromomethyl)benzene peptide chain, add DMF (10 mL / g), and add triethylamine as an acid-binding agent. The mass ratio of triethylamine to triethylamine in S7 is 1:49. Ensure that the entire system is anhydrous and carry out the reaction at 80°C.

[0077] S14: Rinse twice with DMF (10 mL / g), three times with DCM (10 mL / g), and four times with methanol (10 mL / g), then dry under vacuum for 10 min; prepare the cleavage solution (10 mL / g), which, by mass percentage, consists of 94.5% TFA, 2.5% water, 2.5% EDT, and 1% TIS, and cleave for 180 min; dry the lysate with nitrogen, add diethyl ether to precipitate the peptide chain, centrifuge to remove the supernatant, wash the precipitate six times with diethyl ether, and then evaporate to dryness at 25 °C.

[0078] S15: Dissolve 10 mg of crude product in 1 mL of HPLC-grade LACN and 1 mL of water. Analyze 20 μL of the sample on an HPLC instrument to determine the elution time of the target peak. Collect the target peak solution using a C18 reversed-phase chromatography system. Set the HPLC parameters as follows: Wavelength: 220 nm; Flow Rate: 15 mL / min; Inj. Vol: 20 mL; Column Temp: 25 °C; Buffer A: 0.1% TFA in water; Buffer B: 0.1% TFA in Acetonitrile. Lyophilize the target peak solution to obtain the FAP-2286 precursor and store at -20 °C.

[0079] English definition:

[0080] DCM: Dichloromethane;

[0081] DMF: NN-dimethylformamide;

[0082] HBTU: Benzotriazole-N,N,N,N-Tetramethylurea hexafluorophosphate;

[0083] DIEA: N,N-Diisopropylethylamine

[0084] KCN: Potassium cyanide

[0085] TFA: Trifluoroacetic acid

[0086] PyBop: Benzotriazol-1-yl-oxytripyrrolidinyl hexafluorophosphate

[0087] EDT: 1,2-Ethylenedithiol

[0088] TIS: Triisopropylsilane

[0089] All units in the embodiments are based on the dry weight of 2-Chlorotrityl Chloride Resin.

[0090] The third aspect of this embodiment provides an application of a radiolabeled FAP-2286 precursor for tumor imaging.

[0091] The tumor is a solid tumor.

[0092] The solid tumor is a breast tumor.

[0093] The method of application is to combine the FAP-2286 precursor with radioactive iodine.

[0094] Performance testing

[0095] 1. The FAP-2286 precursor was analyzed by MS and HPLC for purity. The purity was 96.4%. The results are shown in the figure. Figure 1 , Figure 2 .

[0096] 2. The FAP-2286 precursor was labeled with radioactive iodine: iodogen iodination reaction. Dichloromethane containing 0.02% chloroglyurea was added to the bottom of the reaction tube, dissolved in PBS, and then radioactive sodium iodide and the FAP-2286 precursor (FAP-2286-tyr) were added and mixed. The mixture was reacted at room temperature for 10 minutes. The conjugate was separated and purified by Sephadex G-50 gel column chromatography to obtain the iodine-labeled FAP-2286 precursor.

[0097] Iodine-labeled FAP-2286 precursor was injected via tail vein into mice bearing breast cancer (4T1 cells). Results are shown in [Figure number missing]. Figure 3 Two hours after injection, the uptake rate of I-131-labeled FAP-2286 in mice was 3.11 ± 0.70%.

[0098] FAP-2286- 68 Ga was injected into mice bearing breast cancer, and imaging was performed 2 hours later. The results are shown in [the table / image]. Figure 4As can be seen from the figure, the imaging agent in this embodiment showed better uptake than FAP-2286 two hours after injection. 68 Ga.

[0099] Iodine-labeled FAP-2286 precursor was injected via the tail vein into mice bearing breast cancer (4T1 cells). Two hours after injection, the uptake rate of I-125-labeled FAP-2286 in the mice was 2.95 ± 0.55%.

[0100] Iodine-labeled FAP-2286 precursor was injected into mice with subcutaneous pancreatic cancer tumors based on PANC02 cells. The uptake rate of the subcutaneous tumors was 9.55 ± 1.31% 2 hours after injection.

Claims

1. A radiolabeled FAP-2286 precursor for use in tumors, characterized in that, Its structural formula is shown in equation (1): Equation (1); The R group is of formula (2); Equation (2).

2. A method for preparing a radiolabeled FAP-2286 precursor for tumor application according to claim 1, characterized in that, S1: Resin swelling: Place 2-Chlorotrityl Chloride Resin into a reaction tube, add DMF 12-18 mL / g, and shake for 55-65 min; S2: Connects to the first amino acid, Fmoc-Cys-OH; S3: Deprotection, detection, and resin rinsing; S4: Condensation, inspection, and resin rinsing; S5: Repeat S3 to S4, connecting amino acids sequentially; S6: Rinse resin, remove protection, rinse resin; S7: Remove solvent and inoculate with 1,3,5-Tris bromomethyl benzen; S8: Rinse the resin to obtain a reaction tube containing a Tris bromomethyl benzen peptide chain; S9: Prepare another reaction tube, add 2-Chlorotrityl Chloride Resin, and inoculate with amino acids; S10: Repeat step S3, then add DOTA-tris tBu ester to react; S11: DOTA-tris tBu ester-Y tbu polypeptide was obtained by cleavage from resin; S12: Dissolve the DOTA-tris tBu ester-Y tbu polypeptide in DCM, add NH2CH2CH2SH, perform PyBop reaction, and then remove the solvent; S13: Dissolve the peptide obtained in S12 and add it to a reaction tube containing a Tris bromomethyl benzen peptide chain for reaction; S14: Rinse the resin, prepare the cutting fluid to cut the peptide chain, and blow dry and wash. S15: Purification and preparation.

3. The method for preparing the radiolabeled FAP-2286 precursor for tumor application according to claim 2, characterized in that, The specific steps of S2 are as follows: filter out the solvent in the reaction tube of S1 by sand core filtration, add 3 parts of excess Fmoc-Cys-OH amino acid (the first amino acid at the C-terminus), add 10 times the excess DIEA, and finally add DMF to dissolve. Shake for 25-35 min, seal with methanol, and let it sit for 25-35 min.

4. The method for preparing the radiolabeled FAP-2286 precursor for tumor application according to claim 2, characterized in that, The deprotection process in S3 is as follows: remove DMF, add 12-18 mL / g of 20% piperidine DMF solution, react for 4-6 min, remove DMF and add 15 mL / g of 20% piperidine DMF solution, react for 10-20 min.

5. The method for preparing the radiolabeled FAP-2286 precursor for tumor application according to claim 2, characterized in that, The detection process in S3 is as follows: remove the piperidine DMF solution, take the resin, wash it with ethanol 3 to 4 times, add one drop each of ninhydrin, KCN, and phenol solution, heat at 105℃ to 110℃ for 5 to 7 minutes, and a deep blue color indicates a positive reaction.

6. The method for preparing the radiolabeled FAP-2286 precursor for tumor application according to claim 2, characterized in that, The process of rinsing the resin in S3, S4, S6, and S8 is as follows: rinse twice with DMF 10 mL / g, rinse twice with methanol 10 mL / g, and rinse twice with DMF 10 mL / g in sequence.

7. The method for preparing the radiolabeled FAP-2286 precursor for tumor application according to claim 2, characterized in that, The specific condensation process in S4 is as follows: add 3 times molar excess of Fmoc to protect amino acids, 3 times molar excess of HBTU, then add 10 times molar excess of DIEA, and finally add DMF to dissolve and shake for 45-50 minutes.

8. The method for preparing the radiolabeled FAP-2286 precursor for tumor application according to claim 2, characterized in that, The amino acids sequentially linked in S5 are Fmoc-Pro-OH, Fmoc-Thr-OH, Fmoc-Gln-OH, and Fmoc-Phe-OH.

9. An application of the radiolabeled FAP-2286 precursor for tumors according to claim 1, characterized in that, It is used to prepare tumor imaging agents, wherein the tumor is a solid tumor.

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