Single Photon Emission Computed Tomography Experience With (S)-5-[123I]Iodo-3-(2-Azetidinylmethoxy)Pyridine in the Living Human Brain of Smokers and Nonsmokers

被引：16

作者：

Brasic, James Robert ^{[1
]}

Zhou, Yun ^{[1
]}

Musachio, John L. ^{[1
]}

Hilton, John ^{[1
]}

Fan, Hong ^{[1
]}

Crabb, Andrew ^{[1
]}

Enders, Cristopher J. ^{[1
]}

Reinhardt, Melvin J. ^{[1
]}

Dogan, Ahmet S. ^{[1
]}

Alexander, Mohab ^{[1
]}

Rousset, Olivier ^{[1
]}

Maris, Marika A. ^{[1
]}

Galecki, Jeffrey ^{[1
]}

Nandi, Ayon ^{[1
]}

Wong, Dean F. ^{[1
]}

机构：

[1] Johns Hopkins Univ, Div Nucl Med, Russell H Morgan Dept Radiol & Radiol Sci, Sch Med,Johns Hopkins Outpatient Ctr, Baltimore, MD 21287 USA

来源：

SYNAPSE | 2009年 / 63卷 / 04期

关键词：

binding; infusions; density; distribution; treatment efficacy; safety; tomography; NICOTINIC ACETYLCHOLINE-RECEPTORS; IN-VIVO; UP-REGULATION; DISCRIMINATIVE STIMULUS; TRANSDERMAL NICOTINE; RADIATION-DOSIMETRY; SECONDHAND SMOKE; ABNORMAL REGULATION; ALZHEIMERS-DISEASE; TOURETTES-SYNDROME;

D O I：

10.1002/syn.20611

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

(S)-5-[I-123]iodo-3-(2-azetidinylmethoxy)pyridine (5-[I-123]IA), a novel potent radioligand for high-affinity alpha 4 beta 2* neuronal nicotinic acetylcholine receptors (nAChRs), provides a means to evaluate the density and the distribution of nAChRs in the living human brain. We sought in healthy adult smokers and nonsmokers to (1) evaluate the safety, tolerability, and efficacy of 5-[I-123]IA in an open nonblind trial and (2) to estimate the density and the distribution of alpha(4)beta(2)* nAChRs in the brain. Single photon emission computed tomography (SPECT) was performed for 5 h after the i.v. administration of similar to 0.001 mu g/kg (similar to 10 mCi) 5-[I-123]IA. Blood pressure, heart rate, and neurobehavioral status were monitored before, during, and after the administration of 5-[I-123]IA to 12 healthy adults (8 men and 4 women) (6 smokers and 6 nonsmokers) ranging in age from 19 to 46 years (mean = 28.25, standard deviation = 8.20). High plasma-nicotine level was significantly associated with low 5-[I-123]IA binding in: (1) the caudate head, the cerebellum, the cortex, and the putamen, utilizing both the Sign and Mann-Whitney U-tests; (2) the fusiform gyrus, the hippocampus, the parahippocampus, and the pons utilizing the Mann-Whitney U-test; and (3) the thalamus utilizing the Sign test. We conclude that 5-[I-123]IA is a safe, well-tolerated, and effective pharmacologic agent for human subjects to estimate high-affinity alpha 4/beta 2 nAChRs in the living human brain. Synapse 63:339-358, 2009. (c) 2009 Wiley-Liss, Inc.

引用

页码：339 / 358

页数：20

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