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Positron emission tomography (PET) is a preclinical and clinical imaging technique extensively used to study and visualize biological and physiological processes in vivo. Fluorine-18 ( 18 F) is the most frequently used positron emitter for PET imaging due to its convenient 109.8 min half-life, high yield production on small biomedical cyclotrons, and well-established radiofluorination chemistry. The presence of fluorine atoms in many drugs opens new possibilities for developing radioligands labelled with fluorine-18. The trifluoromethyl group (CF 3 ) represents a versatile structural motif in medicinal and pharmaceutical chemistry to design and synthesize drug molecules with favourable pharmacological properties. This fact also makes CF 3  groups an exciting synthesis target from a PET tracer discovery perspective. Early attempts to synthesize [ 18 F]CF 3 -containing radiotracers were mainly hampered by low radiochemical yields and additional challenges such as low radiochemical purity and molar activity. However, recent innovations in [ 18 F]trifluoromethylation chemistry have significantly expanded the chemical toolbox to synthesize fluorine-18-labelled radiotracers. This review presents the development of significant [ 18 F]trifluoromethylation chemistry strategies to apply [ 18 F]CF 3 -containing radiotracers in preclinical and clinical PET imaging studies. The continuous growth of PET as a crucial functional imaging technique in biomedical and clinical research and the increasing number of CF 3 -containing drugs will be the primary drivers for developing novel [ 18 F]trifluoromethylation chemistry strategies in the future.

Advances in [18F]Trifluoromethylation Chemistry for PET Imaging