Synthesis of [18F]Fallypride in a Micro-Reactor: Rapid Optimization and Multiple-Production in Small Doses for Micro-PET Studies

Abstract

A commercial coiled-tube micro-reactor (NanoTek; Advion) was used as a convenient platform for the synthesis of [(18)F]fallypride in small doses (0.5-1.5 mCi) for micro-PET studies of brain dopamine subtype-2 receptors in rodents. Each radiosynthesis used low amounts (20-40 mug; 39-77 nmol) of tosylate precursor and [(18)F]fluoride ion (0.5-2.5 mCi). Optimization of the labeling reaction in the apparatus, with respect to the effects of precursor amount, reaction temperature, flow rate and [(18)F]fluoride ion to precursor ratio, was achieved rapidly and the decay-corrected radiochemical yield of [(18)F]fallypride (up to 88%) was reproducible. The low amounts of material used in each radiosynthesis allowed crude [(18)F]fallypride to be purified rapidly on an analytical-size reverse phase HPLC column, preceding formulation for intravenous injection. Scale-up of the reaction was easily achieved by continuously infusing reagent precursor solutions to obtain [(18)F]fallypride in much greater quantity.