Division of Molecular Imaging and Neuropathology, Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
J Pharmacol Sci. 2012;120(3):254-7. doi: 10.1254/jphs.12100sc. Epub 2012 Oct 16.
Serotonin (5-HT) 1A receptors exist in high and low affinity states. Agonist ligands bind preferentially to the high affinity state receptors, providing a more functionally relevant measure than antagonist binding. We now report comparison of 5-HT(1A) binding in vivo using both [¹¹C]CUMI-101 (agonist) and [¹¹C]WAY100635 (antagonist) in nonhuman primates. PET studies show that both tracers bind to known 5-HT(1A) receptor (5-HT(1A)R)-rich regions of baboon brain. The binding (BP(F)) of [¹¹C]CUMI-101 was lower on an average of 55% across the regions of interest (ROIs) compared to [¹¹C]WAY100635. This ratio is consistent with the in vitro binding data of agonist and antagonist 5-HT(1A)R ligands previously reported.
5-HT1A 受体存在高亲和态和低亲和态。激动剂配体优先与高亲和态受体结合，提供比拮抗剂结合更具功能相关性的测量。我们现在报告使用非人类灵长类动物中的 [¹¹C]CUMI-101（激动剂）和 [¹¹C]WAY100635（拮抗剂）进行体内 5-HT1A 结合的比较。PET 研究表明，两种示踪剂都与狒狒大脑中已知的 5-HT1A 受体（5-HT1AR）丰富区域结合。与 [¹¹C]WAY100635 相比，[¹¹C]CUMI-101 在感兴趣区域（ROI）的平均结合（BP(F)）低 55%。该比值与先前报道的激动剂和拮抗剂 5-HT1AR 配体的体外结合数据一致。
