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Titolo:
ALTROPANE, A SPECT OR PET IMAGING PROBE FOR DOPAMINE NEURONS - III - HUMAN DOPAMINE TRANSPORTER IN POSTMORTEM NORMAL AND PARKINSONS DISEASED BRAIN
Autore:
MADRAS BK; GRACZ LM; FAHEY MA; ELMALEH D; MELTZER PC; LIANG AY; STOPA EG; BABICH J; 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 BROWN UNIV,SCH MED PROVIDENCE RI 02912 MASSACHUSETTS GEN HOSP,DEPT RADIOL BOSTON MA 02114
Titolo Testata:
Synapse
fascicolo: 2, volume: 29, anno: 1998,
pagine: 116 - 127
SICI:
0887-4476(1998)29:2<116:AASOPI>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
COCAINE RECOGNITION SITES; CFT )H-3>WIN 35,428; HIGH-AFFINITY; MONKEY BRAIN; BETA-CIT; H-3 CFT; BINDING-SITES; IN-VIVO; SEROTONIN TRANSPORTERS; CAUDATE-NUCLEUS;
Keywords:
DOPAMINE TRANSPORTER; SPECT IMAGING; DOPAMINE NEURONS; PARKINSONS DISEASE; COCAINE; NEURODEGENERATIVE DISEASES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
68
Recensione:
Indirizzi per estratti:
Citazione:
B.K. Madras et al., "ALTROPANE, A SPECT OR PET IMAGING PROBE FOR DOPAMINE NEURONS - III - HUMAN DOPAMINE TRANSPORTER IN POSTMORTEM NORMAL AND PARKINSONS DISEASED BRAIN", Synapse, 29(2), 1998, pp. 116-127

Abstract

Increasing evidence suggests that the dopamine transporter is situated almost exclusively on dopamine neurons. Accordingly, it is an valuable marker for Parkinson's disease and other pathological states of dopamine neurons. We previously demonstrated that the potent dopamine transport inhibitor [I-125]altropane (IACFT:E-N-iodoallyl-2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane) is a high affinity selective probe for the dopamine transporter in monkey brain and an effective SPECT imaging agent in nonhuman primate brain. We now report the binding properties of [I-125]altropane in postmortem tissue of normal human brainand compare the findings to Parkinson's diseased brain. In homogenates of human brain putamen, [I-125]altropane bound with high affinity (K-D: 4.96 +/- 0.38 nM, n = 4) and site density (B-MAX: 212 +/- 41.1 pmol/g original wet tissue weight) well within the density range reportedpreviously for the dopamine transporter in this brain region. Drugs inhibited [I-125]altropane binding with a rank order of potency that corresponded closely to their rank order for blocking dopamine transport(r 0.98, P < 0.001). In postmortem Parkinson's diseased brain, bound [I-125]altropane (1 nM) was markedly reduced (89%, 99% in putamen, depending on measures of nonspecific binding) compared with normal aged-matched controls (normal putamen: 49.2 +/- 8.1 pmol/g; Parkinson's diseased putamen: 0.48 +/- 0.33 pmol/g; n = 4). In vitro autoradiography, conducted in tissue sections at a single plane of the basal ganglia, revealed high levels of [I-125]altropane binding the caudate nucleus and putamen, but lower levels (73% of the caudate-putamen) in the nucleus accumbens (n = 7). In Parkinson's diseased brains (n = 4), [I-125]altropane binding was 13% of the levels detected in normal putamen, 17% of normal values in the caudate nucleus, and 25% of normal levels in nucleus accumbens. The association of [I-125]altropane to the dopamine transporter in human postmortem tissue, the marked reduction of [I-125]altropane binding in Parkinson's diseased brains, its rapid entry into brain and highly localized distribution in dopamine-rich brain regions, support its use as a probe for monitoring the dopamine transporterin vitro and in vivo by SPECT imaging. (C) 1998 Wiley-Liss, Inc.

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Documento generato il 28/03/20 alle ore 12:57:54