A Gas Phase Route to [18F]fluoroform with Limited Molar Activity Dilution

Sci Rep. 2019 Oct 16;9(1):14835. doi: 10.1038/s41598-019-50747-3.

Abstract

Positron emission tomography (PET) is an important imaging modality for biomedical research and drug development. PET requires biochemically selective radiotracers to realize full potential. Fluorine-18 (t1/2 = 109.8 min) is a major radionuclide for labeling such radiotracers but is only readily available in high activities from cyclotrons as [18F]fluoride ion. [18F]fluoroform has emerged for labeling tracers in trifluoromethyl groups. Prior methods of [18F]fluoroform synthesis used difluoro precursors in solution and led to high dilution with carrier and low molar activity (Am). We explored a new approach for the synthesis of [18F]fluoroform based on the radiosynthesis of [18F]fluoromethane from [18F]fluoride ion and then cobaltIII fluoride mediated gas phase fluorination. We estimate that carrier dilution in this process is limited to about 3-fold and find that moderate to high Am values can be achieved. We show that [18F]fluoroform so produced is highly versatile for rapidly and efficiently labeling various chemotypes that carry trifluoromethyl groups, thereby expanding prospects for developing new PET radiotracers.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Chlorofluorocarbons, Methane* / chemical synthesis
  • Chlorofluorocarbons, Methane* / chemistry
  • Fluorine Radioisotopes / chemistry
  • Isotope Labeling
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals* / chemical synthesis
  • Radiopharmaceuticals* / chemistry

Substances

  • Chlorofluorocarbons, Methane
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Fluorine-18
  • fluoroform