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.