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

Abstract

Radiotracers labelled with short-lived fluorine-18 (t1/2 = 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 fluoro-phenyl 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.

An Investigation of (Diacetoxyiodo)arenes as Precursors for Preparing No-Carrier-Added [18F]Fluoroarenes from Cyclotron-Produced [18F]Fluoride Ion

“…4,11,13,15,20 Exceptionally, oxidation of 1-iodo-4-(trifluoromethyl)benzene by peracetic acid gave not the (diacetoxyiodo)arene but the bridged compound μ-oxa-bis[(acetoxyiodo)-4-trifluoromethylbenzene] ( 1s; structure shown in Supporting Information), as characterized by NMR and MS data (see Experimental). Such bridged compounds may arise from hydrolysis of the corresponding (diacetoxyiodo)arenes when they bear a strong electron-withdrawing group.…”

Hypervalent aryliodine compounds as precursors for radiofluorination

“…As a formal anion, tosylate or another organic anion is often preferred over halide to confer good solubility of the salt in the organic solvent to be used for radiofluorination (eg, dimethylformamide [DMF] and acetonitrile [MeCN]). Simple metathesis reactions can be used to replace the anion with the one that is desired . Nonetheless, halide anions have sometimes been found preferable for high radiofluorination yields.…”

Rapid synthesis of maleimide functionalized fluorine‐18 labeled prosthetic group using “radio‐fluorination on the Sep‐Pak” method

“…The same research group has demonstrated high radiochemical conversion using the pyridine derivative by halogen (Cl) exchange . More challenging fluorine‐18 labelings at the meta‐position to prepare 3‐[ 18 F]fluorobenzaldehydes have also been reported by our and other groups from a variety of precursors . Recently, Richarz et al reported fluorine‐18 labeled benzaldehydes according to the “minimalist” radiolabeling protocol, without base and azeotropic drying of [ 18 F]fluoride .…”