SYNTHESIS OF N-TERT-B UTY L-a-(4-[18F] FLUOROPH ENY L)- NITRONE (['*F]FPBN) FOR IN VlVO DETECTION OF FREE RADICALS

We have synthesized the fluorine-I 8 labeled derivative of N-fert-butyl-aphenylnitrone (PBN), a free radical spin trapping agent widely used with electron spin resonance (ESR). N-tert-Butyl-a-(4-[18F]fluorophenyl)nitrone ([18F]FPBN) could be prepared with low radiochemical yield (3% decay corrected) by the direct aromatic nucleophilic substitution of N-tertbutyl-a-(4-nitrophenyl)nitrone with [18F]fluoride. An alternate two step synthesis route consisted of the nucleophilic [18F]fluoride substitution of 4-N,N,N-trimethylammoniumbenzaldehyde triflate to yield 4-[18F]fluorobenzaldehyde, which was distilled into a vial containing N-tert-butylhydroxylamine in 2N NaOH. 4-[18F]Fluorobenzaldehyde readily reacted with the hydroxylamine to form [IBFIFPBN . [18F]FPBN was obtained in overall decay corrected yields of 24% in a total synthesis time c45 min. and was suitable for further applications in in vivo studies of free radicals.