Facile aromatic radiofluorination of [F-18]flumazenil from diaryliodonium salts with evaluation of their stability and selectivity

Abstract

Aromatic radiofluorination of the diaryliodonium tosylate precursor with [F-18]fluoride ions has been applied successfully to access [F-18]flumazenil in high radiochemical yields of 67.2 +/- 2.7% (decay corrected). The stability and reactivity of the diaryliodonium tosylate precursor plays a key role in increasing the production of F-18-labelled molecules under the fluorine-18 labelling condition. Various conditions were explored for the preparation of [F-18]flumazenil from different diaryliodonium tosylate precursors. Optimum incorporation of [F-18]fluoride ions in the 4-methylphenyl-mazenil iodonium tosylate precursor (5f) was achieved at 150 degrees C for 5 min by utilizing 4 mg of the precursor, K-2.2.2/K2CO3 complex, and the radical scavenger in N,N-dimethylformamide. This approach was extended to a viable method for use in automated synthesis with a radiochemical yield of 63.5 +/- 3.2% (decay corrected, n = 26) within 60.0 +/- 1.1 min. [F-18]Flumazenil was isolated by preparative HPLC after the reaction was conducted under improved conditions and exhibited sufficient specific activity of 370-450 GBq mu mol(-1), with a radiochemical purity of >99%, which will be suitable for human PET studies.