Development of microwave-based automated nucleophilic [18F]fluorination system and its application to the production of [18F]flumazenil

IntroductionThis study presents the development of an automated radiosynthesis system integrating a microwave reactor and its subsequent application in the synthesis of [18F]flumazenil, a potentially useful compound in the evaluation of central benzodiazepine receptor density.MethodsPreparation of dry [K/K222]+18F− complex and radiofluorination of the nitro-flumazenil precursor were achieved using the developed microwave-based radiosynthesis system. The crude product was prepurified in a C18 cartridge followed by reversed-phase preparative high-performance liquid chromatography. The isolated [18F]flumazenil was evaporated in vacuo and reconstituted in an ethanol-free solution.ResultsOptimum incorporation of 18F− in the nitro-precursor was achieved in 5 min time utilizing 2 mg of precursor in N,N-dimethylformamide reacted at 160°C which gave an incorporation yield of 40±5%. The radiochemical yield obtained at the end of synthesis was 26±4% (EOB) with a radiochemical purity of >99% and a total synthesis time of about 55–60 min. The produced [18F]flumazenil was observed to be stable for at least 8 h.ConclusionThe developed [18F]flumazenil radiosynthesis system offers shorter reaction time, simplicity in operation and applicability for use in routine clinical practice.