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

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

► The high reactivity of electrochemically concentrated [18F]fluoride was shown.
► Microfluidic radiosynthesis with the [18F]fluoride effectively reduced synthesis time.
► Microfluidic radiosynthesis increased yields of products labile at high temperatures.