Single-step syntheses of no-carrier-added functionalized [18F]fluoroarenes as labeling synthons from diaryliodonium salts

Abstract

Radiotracers labelled with short-lived fluorine-18 (t_1/2 = 109.7 min) are keenly sought for biomedical imaging with positron emission tomography (PET). The radiotracers are mostly required at high specific radioactivities, necessitating their radiosyntheses from cyclotron-produced no-carrier-added [¹⁸F]fluoride ion. PET radiotracers encompass wide structural diversity and molecular weight. Hence, diverse ¹⁸F-labeling methodology is needed to accomplish the required radiosyntheses in a simple and rapid manner. A useful strategy is to introduce nucleophilic [¹⁸F]fluoride ion first into a labeling synthon that may then be applied to label the target radiotracer. Here, we show that various functionalized [¹⁸F]fluoroarenes may be rapidly synthesized as labeling synthons through single-step reactions of appropriate diaryliodonium salts with [¹⁸F]fluoride ion. Decay-corrected radiochemical yields (RCYs) varied with position of functional group, choice of electron-rich aryl ring in the diaryliodonium salt, and choice of anion. Under best conditions, ¹⁸F-labeled fluorobenzaldehydes, fluorobenzyl halides, fluorobenzoic acid esters and fluorophenyl ketones were obtained selectively in 40–73%, 20–55%, 46–89% and 81–98% RCYs, respectively. This versatile straightforward methodology will enhance the scope for producing structurally complex, yet useful, PET radiotracers.