Home List of Titles Synthesis and evaluation in monkey of two sensitive 11C-labeled aryloxyanilide ligands for imaging brain peripheral benzodiazepine receptors in vivo
Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.3/81512
- Synthesis and evaluation in monkey of two sensitive 11C-labeled aryloxyanilide ligands for imaging brain peripheral benzodiazepine receptors in vivo
- Briard, Emmanuelle; Zoghbi, Sami S.; Imaizumi, Masao; Gourley, Jonathan P.; Shetty, H. Umesha; Hong, Jinsoo; Cropley, Vanessa; Fujita, Masahiro; Innis, Robert B.; Pike, Victor W.
- We sought to develop 11C-labeled ligands for sensitive imaging of brain peripheral benzodiazepine receptors (PBR) in vivo. Two aryloxyanilides with high affinity for PBR were identified and synthesized, namely, N-acetyl-N-(2-methoxycarbonylbenzyl)-2-phenoxyaniline (3, PBR01) and N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide (10, PBR28). 3 was hydrolyzed to 4, which was esterified with [11C]iodomethane to provide [11C]3. The O-desmethyl analogue of 10 was converted into [11C]10 with [11C]iodomethane. [11C]3 and [11C]10 were each injected into monkey to assess their brain kinetics with positron emission tomography (PET). After administration of either radioligand there was moderately high brain uptake of radioactivity. Receptor blocking and displacement experiments showed that a high proportion of this radioactivity was bound specifically to PBR. In monkey and rat, 3 and 10 were rapidly metabolized by ester hydrolysis and N-debenzylation, respectively, each to a single polar radiometabolite. [11C]3 and [11C]10 are effective for imaging PBR in monkey brain. [11C]10 especially warrants further evaluation in human subjects.
- Publication type
- Journal article
- Journal of Medicinal Chemistry, Vol. 51, no. 1 (Jan 2008), pp. 17-30
- Publication year
- FOR Code(s)
- 0304 Medicinal and Biomolecular Chemistry; 1115 Pharmacology and Pharmaceutical Sciences
- Aryloxyanilides; Brains; Imaging; In vivo; Monkeys; PBR; Peripheral benzodiazepine receptor
- American Chemical Society
- Publisher URL
- Copyright © 2008.
- Additional information
- This study was supported by the Intramural Research Program of the National Institutes of Health, specifically the National Institute of Mental Health.
- Peer reviewed