Optimization of the synthesis and puri cation of 6-[18F]fluoropiperonal, synton for the preparation of complex molecules used as pet tracers

Abstract

An optimized synthesis method for 6-[18F] uoropiperonal (6-[18F]FP) via nucleophilic sub itution of the nitro group in the precursor molecule (nitropiperonal, 6-NP) with [18F] uoride 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 e cient solid-phase extraction technique on disposable cartridges. 6-[18F]FP was obtained with radiochemical purity of 99% 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 puri cation.