Titania-Catalyzed Radiofluorination of Tosylated Precursors in Highly Aqueous Medium

Nucleophilic radiofluorination is an efficient synthetic route to many positron-emission tomography (PET) probes, but removal of water to activate the cyclotron-produced [18F]­fluoride has to be performed prior to reaction, which significantly increases overall radiolabeling time and causes radioactivity loss. In this report, we demonstrate the possibility of 18F-radiofluorination in highly aqueous medium. The method utilizes titania nanoparticles, 1:1 (v/v) acetonitrile–thexyl alcohol solvent mixture, and tetra-n-butylammonium bicarbonate as a phase-transfer agent. Efficient radiolabeling is directly performed with aqueous [18F]­fluoride without the need for a drying/azeotroping step to significantly reduce radiosynthesis time. High radiochemical purity of the target compound is also achieved. The substrate scope of the synthetic strategy is demonstrated with a range of aromatic, aliphatic, and cycloaliphatic tosylated precursors.