Multistep synthesis of a radiolabeled imaging probe using integrated microfluidics

Microreactor technology has shown potential for optimizing synthetic efficiency, particularly in preparing sensitive compounds. We achieved the synthesis of an [F-18]fluoride-radiolabeled molecular imaging probe, 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG), in an integrated microfluidic device. Five sequential processes-[F-18]fluoride concentration, water evaporation, radiofluorination, solvent exchange, and hydrolytic deprotection-proceeded with high radiochemical yield and purity and with shorter synthesis time relative to conventional automated synthesis. Multiple doses of [F-18[FDG for positron emission tomography imaging studies in mice were prepared. These results, which constitute a proof of principle for automated multistep syntheses at the nanogram to microgram scale, could be generalized to a range of radiolabeled substrates.