SYNTHESIS OF N-TERT-BUTYL-ALPHA-(4-[F-18]FLUOROPHENYL)NITRONE ([F-18]FPBN) FOR IN-VIVO DETECTION OF FREE-RADICALS

We have synthesized the fluorine-18 labeled derivative of N-tert-butyl-alpha-phenylnitrone (PEN), a free radical spin trapping agent widely used with electron spin resonance (ESR). N-tert-Butyl-alpha-(4-[F-18]fluorophenyl)nitrone ([F-18]FPBN) could be prepared with low radiochemical yield (3% decay corrected) by the direct aromatic nucleophilic substitution of N-tert-butyl-alpha-(4-nitrophenyl)nitrone with [F-18]fluoride. An alternate two step synthesis route consisted of the nucleophilic [F-18]fluoride substitution of 4-N,N,N-trimethylammonium benzaldehyde triflate to yield 4-[F-18]fluorobenzaldehyde, which was distilled into a vial containing N-tert-butyl-hydroxylamine in 2N NaOH. 4-[F-18]Fluorobenzaldehyde readily reacted with the hydroxylamine to form [F-18]FPBN. [F-18]FPBN was obtained in overall decay corrected yields of 24% in a total synthesis time <45 min. and was suitable for further applications in in vivo studies of free radicals.