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Titolo:
Carbon-11 epidepride: A suitable radioligand for PET investigation of striatal and extrastriatal dopamine D-2 receptors
Autore:
Langer, O; Halldin, C; Dolle, F; Swahn, CG; Olsson, H; Karlsson, P; Hall, H; Sandell, J; Lundkvist, C; Vaufrey, F; Loch, C; Crouzel, C; Maziere, B; Farde, L;
Indirizzi:
Karolinska Hosp, Dept Clin Neurosci, Psychiat Sect, Karolinska Inst, S-17176 Stockholm, Sweden Karolinska Hosp Stockholm Sweden S-17176 Inst, S-17176 Stockholm, Sweden CEA, Serv Hosp Frederic Joliot, Dept Rech Med, F-91406 Orsay, France CEA Orsay France F-91406 ic Joliot, Dept Rech Med, F-91406 Orsay, France
Titolo Testata:
NUCLEAR MEDICINE AND BIOLOGY
fascicolo: 5, volume: 26, anno: 1999,
pagine: 509 - 518
SICI:
0969-8051(199907)26:5<509:CEASRF>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
POTENTIAL ANTIPSYCHOTIC AGENTS; POSTMORTEM HUMAN BRAIN; I-125 EPIDEPRIDE; ANTIDOPAMINERGIC PROPERTIES; BINDING; IDENTIFICATION; LIGAND;
Keywords:
epidepride; dopamine D-2 receptors; extrastriatal; PET; SPECT; brain;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Halldin, C Karolinska Hosp, Dept Clin Neurosci, Psychiat Sect, Karolinska Inst, S-17176 Stockholm, Sweden Karolinska Hosp Stockholm Sweden S-17176 76 Stockholm, Sweden
Citazione:
O. Langer et al., "Carbon-11 epidepride: A suitable radioligand for PET investigation of striatal and extrastriatal dopamine D-2 receptors", NUCL MED BI, 26(5), 1999, pp. 509-518

Abstract

Epidepride {(S)-(-)-N ([1-ethyl-2-pyrrolidinyl]methyl)-5-iodo-2,3-dimethoxybenzamide} binds with a picomolar affinity (K-i = 24 pM) to the dopamine D-2 receptor. Iodine-123-labeled epidepride has been used previously to study striatal and extrastriatal dopamine D-2 receptors with single photon emission computed tomography (SPECT), Our aim was to label epidepride with carbon-ii for comparative quantitative studies between positron emission tomography (PET) and SPECT. Epidepride was synthesized from its bromo-analogue FLB 457 via the corresponding trimethyl-tin derivative. In an alternative synthetic pathway, the corresponding substituted benzoic acid was reacted withthe optically pure aminomethylpyrrolidine-derivative. Demethylation of epidepride gave the desmethyl-derivative, which was reacted with [C-11]methyl triflate. Total radiochemical yield was 40-50% within a total synthesis time of 30 min. The specific radioactivity at the end of synthesis was 37-111 GBq/mu mol (1,000-3,000 Ci/mmol). Human postmortem whole-hemisphere autoradiography demonstrated dense binding in the caudate putamen, and also in extrastriatal areas such as the thalamus and the neocortex. The binding was inhibited by unlabeled raclopride. PET studies in a cynomolgus monkey demonstrated high uptake in the striatum and in several extrastriatal regions. At 90 min after injection, uptake in the striatum, thalamus and neocortex was about 11, 4, and 2 times higher than in the cerebellum, respectively. Pretreatment experiment with unlabeled raclopride (1 mg/kg) inhibited 50-70% of [C-11]epidepride binding. The fraction of unchanged [C-11]epidepride in monkey plasma determined by a gradient high performance liquid chromatography (HPLC) method was about 30% of the total radioactivity at 30 min after injection of [C-11]epidepride. The availability of [C-11]epidepride allows the PET-verification of the data obtained from quantitation studies with SPECT. (C) 1999 Elsevier Science Inc. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/01/20 alle ore 00:56:47