Reactivity of electrochemically concentrated anhydrous [18F]fluoride for microfluidic radiosynthesis of 18F-labeled compounds

Abstract In order to demonstrate the usefulness of electrochemically concentrated [ 18 F]fluoride the reactivity of the [K + /K.222] 18 F − complex concentrated in an aprotic solvent (ca. 60 μL) was evaluated via nucleophilic 18 F-substitution reactions through radiosynthesis of [ 18 F]FDG, [ 18 F]FMISO, [ 18 F]flumazenil and [ 18 F]fluoromethyl bromide. The substitutions were carried out in a microfluidic reaction flow cell and the effects of reaction time, temperature, precursor concentration and reaction solvent on the 18 F-substitution yields were investigated. The 18 F-fluorination yields for the four 18 F-labeled compounds under optimized conditions (98% for protected [ 18 F]FDG, 80% for protected [ 18 F]FMISO, 20% for [ 18 F]flumazenil and 60% for [ 18 F]fluoromethyl bromide) were comparable to or higher than those obtained by conventional means. In this study it is clearly demonstrated that electrochemically concentrated [ 18 F]fluoride enables microfluidic radiosynthesis by effectively reducing synthesis times and especially by increasing radiochemical yields of products labile at high temperatures.