Efficient aliphatic radiofluorination in a mixed organic solvent system was investigated. This method obviates the time-consuming [18F]fluoride drying step routinely required in the preparation of most fluorine-18 positron emission tomography (PET) radiotracers. The [18F]fluoride ions eluted from a QMA (quaternary ammonium anion exchange) cartridge with phase transfer agents were directly mixed in various organic solvents for subsequent radiofluorination. Herein, we report the azeotropic drying-free radiofluorination of aliphatic substrates and demonstrate the viability of hydrated [18F]fluoride ions in a mixed organic solvent system for obtaining useful radiochemical yields (RCYs). This practical and simple method has demonstrated general applicability to the production of established PET tracers as well as to the rapid assessment and chemical optimization of early-stage potential radiotracers.
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