[(11)C]SA4503 脑内 σ(1)受体体内选择性的再评价：emopamil 结合蛋白的作用。

Re-evaluation of in vivo selectivity of [(11)C]SA4503 to σ(1) receptors in the brain: contributions of emopamil binding protein.

机构信息

Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1, Naka, Itabashi, Tokyo 173-0022, Japan.

出版信息

Nucl Med Biol. 2012 Oct;39(7):1049-52. doi: 10.1016/j.nucmedbio.2012.03.002. Epub 2012 Apr 10.

DOI:10.1016/j.nucmedbio.2012.03.002

PMID:22497960

Abstract

INTRODUCTION

Carbon-11-labeled 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine ([(11)C]SA4503) was shown to be a promising PET ligand for mapping σ(1) receptors, and was applied to human subjects. However, an in vitro study indicated that SA4503 also binds to the emopamil binding protein (EBP), vertebral Δ8-Δ7 sterol isomerase. To our knowledge, no information is available about the possibility of [(11)C]SA4503 binding to EBP in the brain in vivo.

METHODS

To confirm the selectivity of [(11)C]SA4503, we carried out an in vivo blocking experiment using high-affinity EBP and σ(1) selective blocker.

RESULTS

The brain uptake of [(11)C]SA4503 was dose-dependently decreased by SA4503 and the high-affinity σ(1) blockers haloperidol, ifenprodil, and trifluperidol. On the other hand, the effects of the high-affinity EBP blockers tamoxifen and trifluoperazine were negligible.

CONCLUSIONS

Our results confirmed the σ(1)-selective binding of [(11)C]SA4503 in the brain.

摘要

简介

碳-11 标记的 1-[2-(3,4-二甲氧基苯基)乙基]-4-(3-苯基丙基)哌嗪([(11)C]SA4503)被证明是一种有前途的用于映射 σ(1)受体的 PET 配体，并已应用于人体。然而，一项体外研究表明，SA4503 还与埃莫匹仑结合蛋白 (EBP)、椎体 Δ8-Δ7 甾醇异构酶结合。据我们所知，目前尚无关于 [(11)C]SA4503 在体内是否与脑内 EBP 结合的信息。