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Titolo:
ALTROPANE, A SPECT OR PET IMAGING PROBE FOR DOPAMINE NEURONS - II - DISTRIBUTION TO DOPAMINE-RICH REGIONS OF PRIMATE BRAIN
Autore:
MADRAS BK; GRACZ LM; MELTZER PC; LIANG AY; ELMALEH DR; KAUFMAN MJ; FISCHMAN AJ;
Indirizzi:
HARVARD UNIV,NEW ENGLAND REG PRIMATE RES CTR,SCH MED,DEPT PSYCHIAT,1 PINE HILL DR SOUTHBOROUGH MA 01772 ORGANIX INC WOBURN MA 00000 MASSACHUSETTS GEN HOSP,DEPT RADIOL BOSTON MA 02114
Titolo Testata:
Synapse
fascicolo: 2, volume: 29, anno: 1998,
pagine: 105 - 115
SICI:
0887-4476(1998)29:2<105:AASOPI>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
COCAINE RECOGNITION SITES; C-11 BETA-CIT; HIGH-AFFINITY; IN-VIVO; PARKINSONS-DISEASE; I-125 RTI-55; SEROTONIN TRANSPORTERS; NUCLEUS-ACCUMBENS; MONKEY BRAIN; RAT-BRAIN;
Keywords:
DOPAMINE TRANSPORTER; DOPAMINE NEURONS; PARKINSONS DISEASE; COCAINE; WIN 35,428; AGING; SPECT IMAGING; PET IMAGING; NEURODEGENERATIVE DISEASES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
60
Recensione:
Indirizzi per estratti:
Citazione:
B.K. Madras et al., "ALTROPANE, A SPECT OR PET IMAGING PROBE FOR DOPAMINE NEURONS - II - DISTRIBUTION TO DOPAMINE-RICH REGIONS OF PRIMATE BRAIN", Synapse, 29(2), 1998, pp. 105-115

Abstract

The dopamine transporter in brain, localized almost exclusively on dopamine neurons, is an effective window on dopamine neurons. SPECT or PET imaging of the transporter in brain requires selective imaging agents that display appropriate pharmacokinetic properties. We previously reported that [I-125]altropane ([I-125]IACFT,2 beta-carbomethoxy-3 -fluoraphenyl)-n-(1-iodoprop-1-en-3-yl)nortropane) bound with high affinity (Kd: 5.33 nM) to a single site on the dopamine transporter and was selective for dopamine over the serotonin transporter in homogenates of monkey striatum. To determine whether the selective binding of [I-125]altropane is reflected in its brain distribution, the in vitro and ex vivo distribution of [I-125]altropane in squirrel monkey (Saimiri sciureus) brain was determined by quantitative autoradiography of coronal. brain sections. In vitro, [I-125]altropane (2 nM) distribution was discrete and was detectable primarily in the dopamine-rich putamen, caudate nucleus, and nucleus accumbens. The resulting putamen:cerebellumratio exceeded 120:1 (n = 3). The selective in vitro binding of [I-125]altropane to the dopamine transporter, at concentrations approachingits Kd value (Kd: 5.33 nM, a single high affinity site), highlight its suitability for investigating the density of the dopamine transporter in various brain regions in vitro. Ex vivo autoradiography was conducted in monkeys to determine whether the brain distribution of [I-125]altropane in vitro was predictive of its brain distribution pattern after intravenous administration. Thirty minutes after intravenous injection, highest levels of [I-125]altropane (0.3 nmol/kg) were detected in the caudate-putamen and nucleus accumbens and lowest levels in the cerebellum and cortex. The putamen or caudate:cerebellum ratio was ?. SPECT imaging of the brain within 30 min of i.v. injection confirmed the rapid and selective accumulation of [I-123]altropane to the striatum. The selective binding of altropane to the dopamine-rich striatum within 30 min of i.v. administration indicates that it is uniquely suitedfor SPECT or PET imaging of the dopamine transporter and associated dopamine neurons. (C) 1998 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 12:30:24