Optimization of the Synthesis and Purification of 6-[18F]Fluoropiperonal, Synthon for the Preparation of Complex Molecules Used as PET Tracers

Abstract

Abstract An optimized synthesis method for 6-[18F]fluoropiperonal (6-[18F]FP) via nucleophilic substitution of the nitro group in the precursor molecule (nitropiperonal, 6-NP) with [18F]fluoride in the presence of tetrabutylammonium tosylate has been proposed. Using this weakly basic phase transfer catalyst, the amount of initial 6-NP in the reaction was reduced from 4.0 to 0.2 mg with negligible amounts after subsequent treatment of the reaction mixture with a strong base (potassium methoxide). In turn, this made it possible to separate 6-[18F]FP and 6-NP with similar physicochemical properties by a simple and efficient solid-phase extraction technique on disposable cartridges. 6-[18F]FP was fabricated with 99% radiochemical purity and a radiochemical yield of 10%. The content of unreacted 6-NP did not exceed 1 µg/mL, which is comparable to the results of laborious semi-preparative HPLC purification.