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Titolo:
Characterization of [I-123]IDAM as a novel single-photon emission tomography tracer for serotonin transporters
Autore:
Kung, MP; Hou, C; Oya, S; Mu, M; Acton, PD; 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: 844 - 853
SICI:
0340-6997(199908)26:8<844:CO[AAN>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
5-HYDROXYTRYPTAMINE UPTAKE COMPLEX; ANTIDEPRESSANT BINDING-SITES; NOR-BETA-CIT; HUMAN-BRAIN; SELECTIVE LIGAND; H-3 PAROXETINE; UPTAKE INHIBITORS; RAT-BRAIN; I-125 5-IODO-6-NITROQUIPAZINE; C-11 MCN5652;
Keywords:
serotonergic neuron; selective serotonin reuptake inhibitors; receptor binding; autoradiography; brain imaging;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Kung, HF Univ Penn, Dept Radiol, 3700 Market St, Philadelphia, PA 19104 USA Univ Penn 3700 Market St Philadelphia PA USA 19104 , PA 19104 USA
Citazione:
M.P. Kung et al., "Characterization of [I-123]IDAM as a novel single-photon emission tomography tracer for serotonin transporters", EUR J NUCL, 26(8), 1999, pp. 844-853

Abstract

Development of selective serotonin transporter (SERT) tracers for single-photon emission tomography (SPET) is important for studying the underlying pharmacology and interaction of specific serotonin reuptake site inhibitors,commonly used antidepressants, at the SERT sites in the human brain. In search of a new tracer for imaging SERT, IDAM (5-iodo-2-[[2-2-[(dimethylamino)methyl]phenyl]thio]benzyl alcohol) was developed. In vitro characterization of IDAM was carried out with binding studies in cell lines and rat tissuehomogenates. In vivo binding of [I-125]IDAM was evaluated in rats by comparing the uptakes in different brain regions through tissue dissections and ex vivo autoradiography. In vitro binding study showed that IDAM displayed an excellent affinity to SERT sites (K-i=0.097 nM, using membrane preparations of LLC-PK1 cells expressing the specific transporter) and showed more than 1000-fold of selectivity for SERT over norepinehrine and dopamine (expressed in the same LLC-PK1 cells). Scatchard analysis of [I-125]IDAM bindingto frontal cortical membrane homogenates prepared from control or p-chloroamphetamine (PCA)-treated rats was evaluated. As expected, the control membranes showed a Kd value of 0.25 nM+/-0.05 nM and a B-max value of 272+/-30 fmol/ max mg protein, while the PCA-lesioned membranes displayed a similar K-d, but with a reduced B-max (20+/-7 fmol/ mg protein). Biodistribution of[I-125]IDAM (partition coefficient =473; 1-octanol/buffer) in the rat brain showed a high initial uptake (2.44% dose at 2 min after i.v. injection) with the specific binding peaked at 60 min postinjection (hypothalamus-cerebellum/cerebellum =1.75), Ex vivo autoradiographs of rat brain sections (60 min after i.v. injection of [I-125]IDAM) showed intense labeling in severalregions (olfactory tubercle, lateral septal nucleus, hypothalamic and thalamic nuclei, globus pallidus, central gray, superior colliculus, substantianigra, interpeduncular nucleus, dorsal and median raphes and locus coeruleus), which parallel known SERT density. This novel tracer has excellent characteristics for in vivo SPET imaging of SERT in the brain.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 17/01/20 alle ore 20:41:44