Preparation method of radionuclide < 18 > F labeled FAPI compound, compound prepared by same and application of compound

Abstract

The invention discloses a preparation method and application of a radionuclide < 18 > F labeled FAPI compound. The method comprises the following steps: adding a NOTA-FAPI precursor, an acetate buffer solution, anhydrous acetonitrile, an AlCl3 acetate buffer solution and a [< 18 > F] fluorine ion solution into a micro-reaction device with an effect of accurately controlling a reaction process, and carrying out a sealed reaction; color change is accurately detected through a sensor, reaction liquid is continuously introduced into a cooling module in time for cooling, and a reaction system is diluted with deionized water; and introducing the diluted reaction solution into a purification module, separating and purifying by using a C18 column, then leaching by using 50-80% ethanol, and filtering by using a 0.22 [mu] m filter membrane to obtain the target compound Al18F-NOTA-FAPI04 with stable performance.

Description

technical field [0001] The present application relates to the technical field of radiopharmaceutical labeling, and in particular, to a method for preparing a compound of radionuclide 18F-labeled FAPI, the compound prepared and the application thereof. Background technique [0002] Fibroblast activation protein (FAP) is a membrane-anchored peptidase belonging to the dipeptidyl peptidase 4 (DPP4) family with dipeptidyl peptidase and endopeptidase activities. It shares 52% homology with DPP4 at the protein level. FAP can be expressed on the surface of tumor stromal cells, macrophages and tumor cell membranes, and is highly expressed in more than 90% of epithelial tumors. Studies have shown that the expression of FAP protein in healthy tissues is extremely low, and its expression is significantly increased in the pathological state of tissue remodeling and repair sites, involving cardiovascular disease, arthritis, and pulmonary fibrosis and other clinical diseases. FAP directl...

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Problems solved by technology

[0003] The vast majority of FAPI PET imaging reported in the literature is by 68 Ga marked, has the following disadvantages: ① 68 Ge / 68 The Ga generator has a low yield per elution; ②The half-life is short (68min), and the storage time is short, which is not conducive to long-distance transportation; ③When there are many patients to be inspected, multiple productions / multiple generators are required to operate, which is costly and not conducive to operation Radiological Protection of Personnel

[0004] Chinese patent (CN202011085122.7) discloses a 18 The preparation method of the F-labeled biomarker, which adopts precursor compound solutions such as P-FAPI, NOTA-FAPI, NCS-FAPI and 18 f - ions, react under heating conditions to obtain 18 For F-labeled biomarkers, the above reaction is difficult, and it is difficult to ensure complete substitution, and the prepared product has low yield, low purity, and poor stability;

[0005] Chinese patent (CN201710962001.8) also discloses a similar method, which also combines a complex precursor solution with 18 f - Ion mixing reacts by 18 F replaces the hydrogen in the precursor to obtain 18 F-labeled biomarkers, this method also has the above-mentioned shortcomings, and the preparation process of its precursor compound is complicated;

In order to improve the yield and purity of the product, it prepares the precursor solution of the cyclic ligand with strong chelating ability to improve the chelating ability and then improve the yield, purity and stability of the product, but the cyclic ligand The preparation cost of the precursor of the group is relatively high, and in the actual use process, Al 18 F-NOTA-FAPI needs to be ready-to-use and ready-to-use, and the reaction speed of the chelation reaction is relatively fast. If the experiment is only carried out by means of a fixed reaction time, the quality of the obtained product will vary due to the inability to determine the actual reaction end point in different experiments. Inhomogeneous, it is difficult to guarantee the stability, yield and purity of the product

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