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 (18)Ffluoride-radiolabeled molecular imaging probe, 2-deoxy-2-18Ffluoro-D-glucose (18FFDG), in an integrated microfluidic device. Five sequential processes-18Ffluoride concentration, water evaporation, radiofluorination, solvent exchange, and hydrolytic deprotection-proceeded with high radio-chemical yield and purity and with shorter synthesis time relative to conventional automated synthesis. Multiple doses of 18FFDG 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.