The glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) is an important molecule in neurotransmission. We have recently developed the first positron emission tomography (PET) tracer [¹¹C]K-2 to visualize and quantify AMPARs in the living human brain. After injection, [¹¹C]K-2 is hydrolyzed at the terminal amide (and is thus metabolized to a major metabolite, [¹¹C]K-2_OH) within 10 min, representing the PET image in rodents and humans. Here, we found that K-2_OH did not penetrate the cell membrane but slowly passed through the blood brain barrier (BBB) with paracellular transport. Furthermore, major efflux transporters in the BBB did not carry K-2_OH. Logan graphical analysis exhibited reversible binding kinetics of this radiotracer in healthy individuals; these results demonstrated that the PET image of this tracer represents cell surface AMPARs with passive penetration of [¹¹C]K-2_OH through the BBB, resulting in reversible binding kinetics. Thus, PET images with this tracer depict the physiologically crucial fraction of AMPARs.

谷氨酸 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体 (AMPAR) 是神经传递中的重要分子。我们最近开发了第一个正电子发射断层扫描 (PET) 示踪剂 [ ¹¹ C]K-2，用于可视化和量化活人大脑中的 AMPAR。注射后，[ ¹¹ C]K-2 在末端酰胺处水解（并因此在 10 分钟内代谢为主要代谢物 [ ¹¹ C]K-2 _OH），代表啮齿动物和人类的 PET 图像。在这里，我们发现 K-2 _OH没有穿透细胞膜，而是通过细胞旁运输缓慢穿过血脑屏障 (BBB)。此外，BBB 中的主要外排转运蛋白不携带 K-2 _OH. Logan 图形分析显示该放射性示踪剂在健康个体中的可逆结合动力学；这些结果表明，该示踪剂的 PET 图像代表细胞表面 AMPAR，[ ¹¹ C]K-2 _OH通过 BBB被动渗透，导致可逆的结合动力学。因此，带有这种示踪剂的 PET 图像描绘了 AMPAR 的生理关键部分。