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
✍ Scribed by Shui-Yu Lu; Jinsoo Hong; John L. Musachio; Frederick T. Chin; Erik S. Vermeulen; Håkan V. Wikström; Victor W. Pike
- Book ID
- 102366911
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- French
- Weight
- 135 KB
- Volume
- 48
- Category
- Article
- ISSN
- 0022-2135
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✦ Synopsis
1-[2-(4-Fluorobenzoylamino)ethyl]-4-(7-methoxynaphthyl)piperazine (S14506) is one of the most potent and selective agonists at 5-HT 1A receptors. For the purpose of prospective 5-HT 1A 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 =20.4 min) or fluorine-18 (t 1/2 =109.7 min), at different positions. Thus, [O-methyl-11 C]S14506 was obtained in a radiosynthesis time of 35 min by treating O-desmethyl-S14506 with [ 11 C]iodomethane and tetrabutylammonium hydroxide in N,N-dimethylformamide. The overall decay-corrected radiochemical yield (RCY) of [O-methyl-11 C]S14506 ranged between 6 and 24% and the specific activity (SA) between 1343 and 3101 Ci/mmol (mean 2390; n=30). [carbonyl-11 C]S14506 was synthesized through a microwaveenhanced direct coupling of in situ generated [ 11 C]organocarboxymagnesium bromide with amine precursor. RCYs ranged from 10 to 18%. [ 18 F]S14506 was prepared via nucleophilic aromatic fluoridation of the 4-nitro analog in 14-35% RCY and with SA ranging from 1063 to 2302 Ci/mmol (mean 1617; n=14) in a radiosynthesis time of 115 min. Heating the radiofluoridation mixture for 5 min at 1808C in a single mode microwave cavity gave similar RCY and SA to