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Titolo:
Single-photon emission tomography imaging of serotonin transporters in thenon-human primate brain with the selective radioligand [I-123]IDAM
Autore:
Acton, PD; Kung, MP; Mu, M; Plossl, K; Hou, C; Siciliano, M; Oya, S; Kung, HF;
Indirizzi:
Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA Univ Penn PhiladelphiaPA USA 19104 pt Radiol, Philadelphia, PA 19104 USA Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 Pharmacol, Philadelphia, PA 19104 USA
Titolo Testata:
EUROPEAN JOURNAL OF NUCLEAR MEDICINE
fascicolo: 8, volume: 26, anno: 1999,
pagine: 854 - 861
SICI:
0340-6997(199908)26:8<854:SETIOS>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
I-123 BETA-CIT; BLOOD-PLATELETS; ALZHEIMERS-DISEASE; RECEPTOR-BINDING; EATING DISORDERS; H-3 PAROXETINE; C-11 MCN5652; UPTAKE SITES; DEPRESSION; DOPAMINE;
Keywords:
serotonin transporter; selective serotonin reuptake inhibitor; 5-hydroxytryptamine; baboon; single-photon emission tomography;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Acton, PD Univ Penn, Dept Radiol, 3700 Market St,Room 305, Philadelphia, PA 19104 USA Univ Penn 3700 Market St,Room 305 Philadelphia PA USA 19104 USA
Citazione:
P.D. Acton et al., "Single-photon emission tomography imaging of serotonin transporters in thenon-human primate brain with the selective radioligand [I-123]IDAM", EUR J NUCL, 26(8), 1999, pp. 854-861

Abstract

A new radioligand, 5-iodo-2-[[2-2-[(dimethylamino)methyl]phenyl]thio]benzyl alcohol ([I-123]TDAM), has been developed for selective single-photon emission tomography (SPET) imaging of SERT. In vitro binding studies suggest ahigh selectivity of IDAM for SERT (K-i=0.097 nM), With considerably lower affinities for norepinephrine and dopamine transporters (NET K-i= 234 nM and DAT K-i>10 mu M, respectively). In this study the biodistribution of SERTin the baboon brain was investigated in vivo using [I-123]IDAM and SPET imaging. Dynamic sequences of SPET scans were performed on three female baboons (Papio anubis) after injection of 555 MBq of [I-123]IDAM. Displacing doses (1 mg/kg) of the selective SERT ligand (+)McN5652 were administered 90-120 min after injection of [I-123]IDAM. Similar studies were performed usinga NET inhibitor, nisoxetine, and a DAT blocker, methylphenidate. After 60-120 min, the regional distribution of tracer within the brain reflected thecharacteristic distribution of SERT, with the highest uptake in the midbrain area (hypothalamus, raphe nucleus, substantia nigra), and the lowest uptake in the cerebellum tan area presumed free of SERT). Peak specific binding in the midbrain occurred at 120 min, with a ratio to the cerebellum of 1.80+/-0.13. At 30 min, 85% of the radioactivity in the blood was metabolite. Following injection of a competing SERT ligand, (+)McN5652, the tracer exhibited rapid washout from areas with high concentrations of SERT (dissociation rate constant in the midbrain, averaged over three baboons, k(off)=0.025+/-0.002 min(-1)), while the cerebellar activity distribution was undisturbed (washout rate 0.0059+/- 0.0003 min(-1)). Calculation of tracer washout rate pixel-by-pixel enabled the generation of parametric images of the dissociation rate constant. Similar studies using nisoxetine and methylphenidate had no effect on the distribution of [I-123]IDAM in the brain. These results suggest that [I-123]IDAM is suitable for selective SPET imaging of SERTin the primate brain, with high contrast, favorable kinetics, and negligible binding to either NET or DAT.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/01/20 alle ore 14:49:30