RADIOLABELING OF 2-OXOQUAZEPAM WITH ELECTROPHILIC F-18 PREPARED FROM [F-18] FLUORIDE

Electrophilic radiofluorination reagents with greatly improved specific activity (10(2)-10(3)-fold) were successfully used to radiolabel the chemically labile ligand 2-oxoquazepam. [F-18]Fluorine was synthesized in an electrical discharge chamber by exchanging varying amounts of carrier fluorine with high specific activity [F-18]methyl fluoride. Both [F-18]fluorine and acetyl [F-18]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'-F-18]-2-Oxoquazepam was obtained with high chemical and radiochemical purity using SepPak precleaning followed by straight phase HPLC in a total synthesis time of approximate to 1.3-1.5 h. The specific activities for [F-18]F, and the isolated product ranged from 1.5-48.5 (n = 7) and 2.6-16.7 (n = 5) GBq/mu mol at 20 min and 80 min from end-of-bombardment, respectively. This is the first report of the electrophilic fluorination of a neuroreceptor ligand with high specific activity. This study demonstrates the promising potential of these electrophilic fluorinating agents prepared from high specific activity [F-18]fluoride.