Single-step syntheses of no-carrier-added functionalized [18F]fluoroarenes as labeling synthons from diaryliodonium salts.
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 [(18)F]fluoride ion. PET radiotracers encompass wide structural diversity and molecular weight. Hence, diverse (18)F-labeling methodology is needed to accomplish the required radiosyntheses in a simple and rapid manner. A useful strategy is to introduce nucleophilic [(18)F]fluoride ion first into a labeling synthon that may then be applied to label the target radiotracer. Here, we show that various functionalized [(18)F]fluoroarenes may be rapidly synthesized as labeling synthons through single-step reactions of appropriate diaryliodonium salts with [(18)F]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, (18)F-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.
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1003, USA.
Joong-Hyun
JH
Chun
Victor W
VW
Pike
D005462:Fluorine Radioisotopes; D007553:Isotope Labeling; D015394:Molecular Structure; D009861:Onium Compounds / Q000138:chemical synthesis / Q000737:chemistry*
D005462:Fluorine Radioisotopes; D009861:Onium Compounds; C007517:diphenyleneiodonium