Alternative methods for labeling the 5-HT1A receptor agonist, 1-[2-(4-fluorobenzoylamino)ethyl]-4-(7-methoxynaphthyl)piperazine (S14506), with carbon-11 or fluorine-18

1-[2-(4-Fluorobenzoylamino)ethyl]-4-(7-methoxynaphthyl)piperazine (S14506) is one of the most potent and selective agonists at 5-HT1A receptors. For the purpose of prospective 5-HT1A receptor imaging with positron emission tomography and the investigation of radioligand metabolic pathways, S14506 was labeled with a positron emitter, either carbon-11 (t(1/2)=20.4min) or fluorine-18 (t(1/2)=109.7min), at different positions. Thus, [O-methyl-C-11]S14506 was obtained in a radiosynthesis time of 35min by treating O-desmethyl-S14506 with [C-11]iodomethane and tetrabutylammonium hydroxide in N,N-dimethylformamide. The overall decay-corrected radiochemical yield (RCY) of [O-methyl-C-11]S14506 ranged between 6 and 24% and the specific activity (SA) between 1343 and 3101 Ci/mmol (mean 2390; n=30). [carbonyl-C-11]S14506 was synthesized through a microwave-enhanced direct coupling of in situ generated [C-11]organocarboxymagnesium bromide with amine precursor. RCYs ranged from 10 to 18%. [F-18]S14506 was prepared via nucleophilic aromatic fluoridation of the 4-nitro analog in 14 35% RCY and with SA ranging from 1063 to 2302Ci/mmol (mean 1617; n=14) in a radiosynthesis time of 115min. Heating the radiofluoridation mixture for 5min at 180 degrees C in a single mode microwave cavity gave similar RCY and SA to heating for 30 min in an oil bath at the same temperature. Copyright (c) 2005 John Wiley & Sons, Ltd.