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.
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