Exploring

The presence of the trifluoromethyl aromatic (Ar-CF3) moiety can enhance the interactions with targets, membrane permeability, metabolic stability, and drug efficacy. It also prioritizes positron emission tomography (PET) imaging without altering original drug structures. Although the simplicity of 18F/19F isotope exchange has flourished in boron-, silicon-, phosphorus- and sulfur-based 18F-radiochemistry, its application to CF2(sp3)-18F bond formation remains challenging. Herein, we reported the radiolabeling of Ar-CF3 derivatives via 18F/19F isotopic exchange across a range of substrates (13 examples), achieving favorable nondecay corrected radiochemical yields (up to 27.2 ± 1.3%) and molar activities (2.8 ± 0.2 GBq·μmol-1). The utility of this isotopic exchange-based strategy for trifluoromethylated arene molecules was further demonstrated through the radiolabeling of other Ar-CF3-containing molecules including ponatinib, and through PET imaging using 18F-labeled selinexor. Overall, this in situ 18F-radiolabeling strategy for Ar-CF3-containing small molecules expands the scope for developing new PET tracers, demonstrates potential application in drug discovery, and offers an efficient approach for synthesizing small-molecule tracers for PET imaging.