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Titolo:
A novel serotonin transporter ligand: (5-iodo-2-(2-dimethylaminomethylphenoxy)-benzyl alcohol
Autore:
Zhuang, ZP; Choi, SR; Hou, C; Mu, M; Kung, MP; 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:
NUCLEAR MEDICINE AND BIOLOGY
fascicolo: 2, volume: 27, anno: 2000,
pagine: 169 - 175
SICI:
0969-8051(200002)27:2<169:ANSTL(>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON EMISSION TOMOGRAPHY; NOREPINEPHRINE UPTAKE SITES; I-123 IDAM; SELECTIVE LIGAND; UPTAKE COMPLEX; HUMAN BRAIN; POTENT; RADIOPHARMACEUTICALS; RADIOLIGAND; SENSITIVITY;
Keywords:
brain imaging agents; antidepressants; radioiodination; SPECT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Kung, HF Univ Penn, Dept Radiol, 3700 Market St,Room 305, Philadelphia, PA19104 USA Univ Penn 3700 Market St,Room 305 Philadelphia PA USA 19104 4 USA
Citazione:
Z.P. Zhuang et al., "A novel serotonin transporter ligand: (5-iodo-2-(2-dimethylaminomethylphenoxy)-benzyl alcohol", NUCL MED BI, 27(2), 2000, pp. 169-175

Abstract

The serotonin transporters (SERT) are the primary binding sites for selective serotonin reuptake inhibitors, commonly used antidepressants such as fluoxetine, sertraline, and paroxetine. Imaging of SERT with positron emission tomography and single photon emission computed tomography in humans wouldprovide a useful tool for understanding how alterations of this system arerelated to depressive illnesses and other psychiatric disorders. In this article the synthesis and characterization of [I-125]ODAM [(5-iodo-2-( 2-dimethylaminomethylphenoxy)-benzyl alcohol, 9)] as an imaging agent in the evaluation of central nervous system SERT are reported. A new reaction scheme was developed for the preparation of compound 9, ODAM, and the corresponding tri-n-butyltin derivative 10. Upon reacting 10 with hydrogen peroxide andsodium[I-125]iodide, the radiolabeled [I-125]9 was Obtained in good yield (94% yield, radiochemical purity >95%). In an initial binding study using cortical membrane homogenates of rat brain, ODAM displayed a good binding affinity with a value of K-i = 2.8 +/- 0.88 nM. Using LLC-PK1 cells specifically expressing the individual transporter (i.e. dopamine [DAT], norepinephrine [NET], and SERT, respectively), ODAM showed a strong inhibition on SERT(K-i = 0.12 +/- 0.02 nM). Inhibition constants for the other two transporters were lower (K-i = 3.9 +/- 0.7 mu M and 20.0 +/- 1.9 nM for DAT and NET,respectively). Initial biodistribution study in rats after an intravenous (IV) injection of [I-125]ODAM showed a rapid brain uptake and washout (2.03, 1.49, 0.79, 0.27, and 0.07% dose/organ at 2, 30, 60, 120, and 240 min, respectively). The hypothalamus region where the serotonin neurons are located exhibited a high specific uptake. Ratios of hypothalamus-cerebellum/cerebellum based on percent dose per gram of these two regions showed values of 0.35, 0.86, 0.86, 0.63, and 0.34 at 2, 30, 60, 120, and 240 min, post-IV injection, respectively. The specific uptake in hypothalamus can be effectively blocked by pretreatment of known SERT ligands. The results suggest that this novel ligand displays desirable in vitro and in vivo properties as a potential SERT imaging agent. NUCL MED BIOL 27;2:169-175, 2000. 9 (C) 2000 Elsevier Science Inc. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 18:39:00