[18F]Fluoromethyl iodide ([18F]FCH2I): preparation and reactions with phenol, thiophenol, amide and amine functional groups

In this study, we report the synthesis and reactivity of [18F]fluoromethyl iodide ([18F]FCH2I) with various nucleophilic substrates and the stabilities of [18F]fluoromethylated compounds. [18F]FCH2I was prepared by reacting diiodomethane (CH2I2) with [18F]KF, and purified by distillation in radiochemical yields of 14–31% (n = 25). [18F]FCH2I was stable in organic solvents commonly used for labeling and aqueous solution with pH 1–7, but was unstable in basic solutions. [18F]FCH2I displayed a high reactivity with various nucleophilic substrates such as phenol, thiophenol, amide and amine. The [18F]fluoromethylated compounds synthesized by the reactions of phenol, thiophenol and tertiary amine with [18F]FCH2I were stable for purification, formulation and storage. In contrast, the [18F]fluoromethylated compounds synthesized by the reactions of primary or secondary amines, and amide with [18F]FCH2I were too unstable to be detected or purified from the reaction mixtures. Defluorination of these [18F]fluoromethyl compounds was a main decomposition route.