Imaging the serotonin transporter with positron emission tomography:: initial human studies with [11C]DAPP and [11C]DASB

被引:230
作者
Houle, S
Ginovart, N
Hussey, D
Meyer, JH
Wilson, AA
机构
[1] Ctr Addict & Mental Hlth, Vivian Rakoff PET Ctr, Toronto, ON M5T 1R8, Canada
[2] Univ Toronto, Toronto, ON, Canada
关键词
positron emission tomography; serotonin transporter; substituted phenylthiobenzylamines; DAPP; DASB;
D O I
10.1007/s002590000365
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
Two novel radioligands, N,N-dimethyl-2-(2-amino-4-methoxyphenyl thio)benzylamine (DAPP) and (N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine (DASB), were radiolabeled with carbon-ii and evaluated as in vivo probes of the serotonin transporter (SERT) using positron emission tomography (PET). Both compounds are highly selective, with nanomolar affinity for the serotonin transporter and micromolar affinity for the dopamine and norepinephrine transporters. Six volunteers were imaged twice, once with each of the two radioligands. Both ligands displayed very good brain penetration and selective retention in regions rich in serotonin reuptake sites. Both had similar brain uptake and kinetics, but the cyano analogue, [C-11]DASB, had a slightly higher brain penetration in all subjects. Plasma analysis revealed that both radiotracers were rapidly metabolized to give mainly hydrophilic species as determined by reverse-phase high-performance liquid chromatography. Inhibition of specific binding to the SERT was demonstrated in three additional subjects imaged with [C-11]DASB following an oral dose of the selective serotonin reuptake blocker citalopram. These preliminary studies indicate that both these substituted phenyl-thiobenzylamines have highly suitable characteristics for probing the serotonin reuptake system with PET in humans.
引用
收藏
页码:1719 / 1722
页数:4
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