Synthesis of [¹⁸F]Fluoroform with High Molar Activity

Fluoroform is an interesting motif for the isotopologue labelling of biologically active compounds with fluorine-18 for PET imaging. However, so far the building block [¹⁸F]fluoroform and consequently the [¹⁸F]trifluoromethylated products suffered from low molar activities ranging from 0.1 to 30 GBq/µmol due to isotopic dilution under the strongly basic standard radiofluorination conditions. In this article the synthesis of high molar activity [¹⁸F]fluoroform is described. By implementing a recently reported novel radiofluorination reagent, [¹⁸F]triflyl fluoride, the concentration of base-cryptand complex in the reaction could be reduced 100-fold compared to standard radiofluorination conditions and molar activities close to 100 GBq/µmol (at end of [¹⁸F]fluoroform synthesis) could be obtained, enabling the imaging of low density receptors. Furthermore, an automated procedure was developed on the commercially available NEPTIS® perform synthesizer to provide access of high molar activity [¹⁸F]fluoroform to other PET centres.