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[11C]K-2 image with positron emission tomography represents cell surface AMPA receptors
Neuroscience Research ( IF 2.4 ) Pub Date : 2021-05-24 , DOI: 10.1016/j.neures.2021.05.009
Tetsu Arisawa 1 , Tomoyuki Miyazaki 1 , Wataru Ota 1 , Akane Sano 1 , Kumiko Suyama 1 , Yuuki Takada 1 , Takuya Takahashi 1
Affiliation  

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-2OH) within 10 min, representing the PET image in rodents and humans. Here, we found that K-2OH 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-2OH. 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-2OH through the BBB, resulting in reversible binding kinetics. Thus, PET images with this tracer depict the physiologically crucial fraction of AMPARs.



中文翻译:

[11C]K-2图像与正电子发射断层扫描代表细胞表面AMPA受体

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。

更新日期:2021-05-24
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