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 (t(1/2) = 109.8 min) is a major radionuclide for labeling such radiotracers but is only readily available in high activities from cyclotrons as [(18)F]fluoride ion. [(18)F]fluoroform has emerged for labeling tracers in trifluoromethyl groups. Prior methods of [(18)F]fluoroform synthesis used difluoro precursors in solution and led to high dilution with carrier and low molar activity (A(m)). We explored a new approach for the synthesis of [(18)F]fluoroform based on the radiosynthesis of [(18)F]fluoromethane from [(18)F]fluoride ion and then cobalt(III) 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 A(m) values can be achieved. We show that [(18)F]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.