Clinical single-tube fluorine-18 multifunctional module equipment and radiopharmaceutical synthesis process

Abstract

The invention relates to clinical single-tube fluorine 18 multifunctional module equipment and a radiopharmaceutical synthesis process. The clinical single-tube fluorine 18 multifunctional module equipment comprises a fluorine-18 ioncapturing and releasingmodule, a high performance liquid chromatography column purification module and a product collection module, wherein the high performance liquidchromatography column purification module adopts liquid for intravenous injection as an HPLC mobile phase; a QMA column of the fluorine-18 ion capturing and releasing module captures fluorine-18 ionsgenerated from an accelerator, and the leacheate of the QMA column and a prodrug respectively enter a reaction tube for mixing with the HPLC mobile phase; the reaction tube is connected with an HPLCseparation column of the high performance liquid chromatography column purification module; the HPLC separation column is connected with the product collection module; and a product having been subjected to online dilution and sterile filtration membrane treatment can be used for intravenous injection. By adopting the equipment and the process provided by the invention, solvent conversion used bya common module can be avoided, a target compound can be correctly collected, the pH value and the radioactive concentration of the product can be adjusted on line, and the process is suitable for full-automatic preparation of clinically common positron emission drugs under a GMP condition.

Description

technical field [0001] The invention belongs to the synthesis technology of fluorine-18-labeled radiopharmaceuticals, in particular to a clinical single-tube fluorine-18 multifunctional modular equipment and a radiopharmaceutical synthesis process. Background technique [0002] 18 F-FDG is currently the most widely used radiopharmaceutical, and is widely used in the diagnosis of various common diseases. but 18 F-FDG is glucose metabolism, which only reflects the uptake and retention of glucose in organs and tumors. There are many deficiencies in practical clinical applications, such as deficiencies in tumor receptors, tumor proliferation, and cellular hypoxia imaging. There is an urgent need for other positron radiopharmaceuticals to make up for 18 Inadequacy of F-FDG. Several specific positron radiopharmaceuticals, such as those for prostate cancer, have been reported in the literature: 18 Imaging drugs for F-DCFPyL and Aβ deposition in the brain 18 F-AV1, cellular hy...

AI Technical Summary

Problems solved by technology

[0004] 1. Based on 18 F-FDG synthesis, the module that assists the HPLC separation system, adopts a separate nucleophilic synthesis and purification system, which cannot effectively integrate the whole process of synthesis, separate operations in the operation, and there is a disconnection phenomenon, and new drugs cannot be developed independently in the later stage

[0005] 2. The powerful All-In-One module synthesizes different nuclides on the same module, and there is a problem of mutual contamination of nuclides, which does not meet the GCP requirements for drug synthesis; at the same time, there is a phenomenon of valve waste due to multiple valve combinations

[0007] 4. All the above modules measure the radioactivity of the product outlet pipeline during HPLC separation, and there is no display for the distribution and residue of radioactivity on the HPLC column, and it is impossible to warn the radioactive peak of the product

Especially when there are multiple side reactions, when a large radioactivity peak is detected in the time-activity curve of the product (such as figure 1 As shown, at Rt=10.2min, a radioactivity peak occurs), it is impossible to judge whether it is a product or an impurity

[0008] At the same time, the volume of the product cannot be calculated according to the radioactivity peak, and there is no way to correctly adjust the pH of the final product and estimate the radiochemical purity of the product, which is usually done manually in the later stage

[0009] 5. After the final product is sterilized by a sterile filter membrane, due to the certain lipophilicity of the product, more radioactivity remains on the sterile filter membrane, generally around 5%, and some are as high as 20%, resulting in a decrease in synthesis efficiency At the same time, in order to verify the integrity of the sterile filter membrane after use, it is necessary to take the sterile filter membrane out of the hot chamber immediately after use to measure whether it is complete, and this operation causes additional radiation doses to the staff

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