Radiolabelling of 2-oxoquazepam with electrophilic 18F prepared from [18F]fluoride

Electrophilic radiofluorination reagents with greatly improved specific activity (102–103-fold) were successfully used to radiolabel the chemically labile ligand 2-oxoquazepam. [18F]Fluorine was synthesized in an electrical discharge chamber by exchanging varying amounts of carrier fluorine with high specific activity [18F]methyl fluoride. Both [18F]fluorine and acetyl [18F]hypofluorite were investigated in the fluoro-destannylation, but the latter was found to give better radiochemical conversions (up to 38%). Isolation procedures were greatly facilitated by the lower masses used. [2′-18F]-2-Oxoquazepam was obtained with high chemical and radiochemical purity using SepPak precleaning followed by straight phase HPLC in a total synthesis time of ≈1.3–1.5 h. The specific activities for [18F]F2 and the isolated product ranged from 1.5–48.5 (n=7) and 2.6–16.7 (n=5) GBq/μmol at 20 min and 80 min from end-of-bombardment, respectively. This is the first report of the electrophilic fluorination of a neuro-receptor ligand with high specific activity. This study demonstrates the promising potential of these electrophilic fluorinating agents prepared from high specific activity [18F]fluoride.