Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1, Naka, Itabashi, Tokyo 173-0022, Japan.
Nucl Med Biol. 2012 Oct;39(7):1049-52. doi: 10.1016/j.nucmedbio.2012.03.002. Epub 2012 Apr 10.
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.
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.
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.
Our results confirmed the σ(1)-selective binding of [(11)C]SA4503 in the brain.
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。
为了确认 [(11)C]SA4503 的选择性，我们使用高亲和力的 EBP 和 σ(1)选择性抑制剂进行了体内阻断实验。
SA4503 和高亲和力的 σ(1) 阻滞剂氟哌啶醇、ifenprodil 和三氟哌啶醇可剂量依赖性地降低 [(11)C]SA4503 的脑摄取。另一方面，高亲和力 EBP 阻滞剂他莫昔芬和三氟拉嗪的作用可以忽略不计。
我们的结果证实了 [(11)C]SA4503 在大脑中的 σ(1)选择性结合。
