[ 18 F]fluoride Activation and 18 F-Labelling in Hydrous Conditions-Towards a Microfluidic Synthesis of PET Radiopharmaceuticals.

18 F-labelled radiopharmaceuticals are indispensable in positron emission tomography. The critical step in the preparation of 18 F-labelled tracers is the anhydrous F-18 nucleophilic substitution reaction, which involves [ 18 F]F - anions generated in aqueous media by the cyclotron. For this, azeotropic drying by distillation is widely used in standard synthesisers, but microfluidic systems are often not compatible with such a process. To avoid this step, several methods compatible with aqueous media have been developed. We summarised the existing approaches and two of them have been studied in detail. [ 18 F]fluoride elution efficiencies have been investigated under different conditions showing high 18 F-recovery. Finally, a large scope of precursors has been assessed for radiochemical conversion, and these hydrous labelling techniques have shown their potential for tracer production using a microfluidic approach, more particularly compatible with iMiDEV™ cassette volumes.