Re-evaluation of in vivo selectivity of [11C]SA4503 to σ1 receptors in the brain: Contributions of emopamil binding protein

IntroductionCarbon-11-labeled 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine ([11C]SA4503) was shown to be a promising PET ligand for mapping σ1 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 [11C]SA4503 binding to EBP in the brain in vivo.MethodsTo confirm the selectivity of [11C]SA4503, we carried out an in vivo blocking experiment using high-affinity EBP and σ1 selective blocker.ResultsThe brain uptake of [11C]SA4503 was dose-dependently decreased by SA4503 and the high-affinity σ1 blockers haloperidol, ifenprodil, and trifluperidol. On the other hand, the effects of the high-affinity EBP blockers tamoxifen and trifluoperazine were negligible.ConclusionsOur results confirmed the σ1-selective binding of [11C]SA4503 in the brain.