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Titolo:
New halogenated [C-11]WAY analogues, [C-11]6FPWAY and [C-11]6BPWAY - Radiosynthesis and assessment as radioligands for the study of brain 5-HT1A receptors in living monkey
Autore:
Sandell, J; Halldin, C; Pike, VW; Chou, YH; Varnas, K; Hall, H; Marchais, S; Nowicki, B; Wikstrom, HV; Swahn, CG; Farde, L;
Indirizzi:
Karolinska Hosp, Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden Karolinska Hosp Stockholm Sweden S-17176 Sect, S-17176 Stockholm, Sweden Hammersmith Hosp, Imperial Coll, Sch Med, MRC,Cyclotron Unit, London W12 0NN, England Hammersmith Hosp London England W12 0NN on Unit, London W12 0NN, England Univ Groningen, Univ Ctr Pharm, Dept Med Chem, NL-9713 AV Groningen, Netherlands Univ Groningen Groningen Netherlands NL-9713 AV V Groningen, Netherlands
Titolo Testata:
NUCLEAR MEDICINE AND BIOLOGY
fascicolo: 2, volume: 28, anno: 2001,
pagine: 177 - 185
SICI:
0969-8051(200102)28:2<177:NH[A[A>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSTMORTEM HUMAN BRAIN; IN-VIVO EVALUATION; AUTORADIOGRAPHIC LOCALIZATION; RADIOACTIVE METABOLITES; SEROTONIN RECEPTORS; HUMAN PLASMA; PET; WAY-100635; BINDING; POTENT;
Keywords:
5-HT1A receptor; radioligand; [C-11]6FPWAY; [C-11]6BPWAY; human brain autoradiography; PET; monkey brain;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Sandell, J Karolinska Hosp, Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden Karolinska Hosp Stockholm Sweden S-17176 76 Stockholm, Sweden
Citazione:
J. Sandell et al., "New halogenated [C-11]WAY analogues, [C-11]6FPWAY and [C-11]6BPWAY - Radiosynthesis and assessment as radioligands for the study of brain 5-HT1A receptors in living monkey", NUCL MED BI, 28(2), 2001, pp. 177-185

Abstract

[Carbonyl-C-11]WAY-100635 ([C-11]WAY) is an established radioligand for the study of brain serotonin(1A) (5-HT1A) receptors in living animals and humans with positron emission tomography (PET). There is a recognised need to develop halogenated ligands for 5-HT1A receptors, either for labelling withlonger lived fluorine-18 for more widespread application with PET or with iodine-123 for application with single photon emission tomography (SPET). Here we used autoradiography and PET to assess two new halogenated anlogues of WAY, namely 6BPWAY and 6FPWAY [N-(2-(1-(4-(2-methoxyphenyl)-piperazinyl)ethyl))-N-(2-(6-bromo-/fluoro-pyridinyl))cyclohexanecarboxamide] as prospective radioligands, initially using carbon-11 as the radiolabel. Labelling of 6BPWAY and 6FPWAY with carbon-11 was accomplished by acylation of the corresponding secondary amine precursors with [carbonyl-C-11]cyclohexanecarbonyl chloride. After incubation of human brain crysections with [C-11]6BPWAYor [C-11]6FPWAY, the highest accumulation of radioactivity was observed incortical areas and the hippocampal formation. Both radioligands had high nonspecific binding. There was a rapid accumulation of radioactivity in the monkey brain after intravenous injection of [C-11]6BPWAY and [C-11]6FPWAY. High accumulation of radioactivity was observed in the frontal and temporalcortex and the raphe nuclei, areas known to contain a high density of 5-HT1A receptors. The ratios of radioactivity in receptor-rich temporal cortex to that in receptor poor cerebellum at peak equilibrium were 1.9 (at 10 min) and 3.0 at (at 20 min) for [C-11]6BPWAY and [C-11]6FPWAY, respectively. In pretreatment experiments with high doses of unlabelled WAY, the level of radioactivity in the frontal and temporal cortex and the raphe nuclei was reduced to the same level as in the cerebellum. Radioactive metabolites of [C-11]6FPWAY appeared at a rate similar to those for [C-11]WAY, with 17% of the radioactivity in plasma represented by unchanged radioligand after 40 min. Radioactive metabolites of [C-11]6BPWAY appeared much more slowly. At 40 min after injection 45% of the radioactivity in plasma still represented unchanged radioligand. The results indicate that 6-pyridinyl radiohalogented analogues of WAY are new leads to radioligands for PET or SPET. (C) 2001 Elsevier Science Inc. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 17/01/20 alle ore 20:14:59