Advances in [18F]Trifluoromethylation Chemistry for PET Imaging

Molecules. 2021 Oct 27;26(21):6478. doi: 10.3390/molecules26216478.


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 (18F) 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 (CF3) represents a versatile structural motif in medicinal and pharmaceutical chemistry to design and synthesize drug molecules with favourable pharmacological properties. This fact also makes CF3 groups an exciting synthesis target from a PET tracer discovery perspective. Early attempts to synthesize [18F]CF3-containing radiotracers were mainly hampered by low radiochemical yields and additional challenges such as low radiochemical purity and molar activity. However, recent innovations in [18F]trifluoromethylation chemistry have significantly expanded the chemical toolbox to synthesize fluorine-18-labelled radiotracers. This review presents the development of significant [18F]trifluoromethylation chemistry strategies to apply [18F]CF3-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 CF3-containing drugs will be the primary drivers for developing novel [18F]trifluoromethylation chemistry strategies in the future.

Keywords: fluorine-18; positron emission tomography (PET); trifluoromethylation chemistry.

Publication types

  • Review

MeSH terms

  • Animals
  • Chemistry Techniques, Synthetic*
  • Fluorine Radioisotopes* / chemistry
  • Humans
  • Isotope Labeling
  • Molecular Structure
  • Positron-Emission Tomography / methods*
  • Radiochemistry
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / chemistry*


  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Fluorine-18