A new procedure for labeling alkylbenzenes with [ 18F]fluoride

Abstract

A new procedure for labeling alkylbenzenes with no-carrier-added (nca) [ 18F]fluoride is reported. This will allow the use of [ 18F]-for-nitro aromatic nucleophilic displacement reaction for labeling aromatic compounds with no activating groups on the benzene ring. The new procedure involves (A) the [ 18F]-for-nitro displacement reaction on nitrophenones, and (B) the reduction of [ 18F]fluorophenones with triethylsilane and trifluoroacetic acid to alkylfluorobenzenes. The desired 18F-labeled alkylbenzenes were prepared in a synthesis time of 1 h with a radiochemical yield of 20% at end-of-synthesis. The procedure has been successfully applied to the synthesis of 18F-labeled alkylating agents, such as 4-[ 18F]fluorophenethyl bromide, 4, and 4-[ 18F]fluorophenbutyl chloride, 5. Using the reaction of piperidine and 4 as a model, the potential use of phenethylbromide 4 for labeling biologically important amines was examined. Initial results indicated that the desired alkylated piperidine was formed in low yields (<5%) due to the conversion of halide 4 to [ 18F]fluorostyrene (>85%) under basic conditions. The new procedure provides an easy method of labeling alkylbenzenes with fluorine-18.