Although aberrations in the number and function of glutamate AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors are thought to underlie neuropsychiatric disorders, no methods are currently available for visualizing AMPA receptors in the living human brain. Here we developed a positron emission tomography (PET) tracer for AMPA receptors. A derivative of 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluoro-phenoxyacetamide radiolabeled with ¹¹C ([¹¹C]K-2) showed specific binding to AMPA receptors. Our clinical trial with healthy human participants confirmed reversible binding of [¹¹C]K-2 in the brain according to Logan graphical analysis (UMIN000020975; study design: non-randomized, single arm; primary outcome: dynamics and distribution volumes of [¹¹C]K-2 in the brain; secondary outcome: adverse events of [¹¹C]K-2 during the 4–10 d following dosing; this trial met prespecified endpoints). In an exploratory clinical study including patients with epilepsy, we detected increased [¹¹C]K-2 uptake in the epileptogenic focus of patients with mesial temporal lobe epilepsy, which was closely correlated with the local AMPA receptor protein distribution in surgical specimens from the same individuals (UMIN000025090; study design: non-randomized, single arm; primary outcome: correlation between [¹¹C]K-2 uptake measured with PET before surgery and AMPA receptor protein density examined by biochemical study after surgery; secondary outcome: adverse events during the 7 d following PET scan; this trial met prespecified endpoints). Thus, [¹¹C]K-2 is a potent PET tracer for AMPA receptors, potentially providing a tool to examine the involvement of AMPA receptors in neuropsychiatric disorders.

尽管谷氨酸 AMPA（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸）受体的数量和功能异常被认为是神经精神疾病的基础，但目前还没有方法可用于观察活人体内的 AMPA 受体脑。在这里，我们开发了一种用于 AMPA 受体的正电子发射断层扫描 (PET) 示踪剂。^用11 C ([ ¹¹ C]K-2)放射性标记的 4-[2-(苯磺酰基氨基)乙硫基]-2,6-二氟-苯氧基乙酰胺衍生物显示出与 AMPA 受体的特异性结合。我们与健康人类参与者的临床试验证实了 [ ¹¹根据 Logan 图形分析 (UMIN000020975) 在大脑中的 C]K-2；研究设计：非随机、单臂；主要结果：[ ¹¹ C]K-2 在大脑中的动力学和分布体积；次要结果：不良事件[ ¹¹ C]K-2 在给药后 4-10 天；该试验达到了预先指定的终点）。在一项包括癫痫患者的探索性临床研究中，我们检测到内侧颞叶癫痫患者的癫痫病灶中[ ¹¹ C]K-2 摄取增加，这与同一手术标本中的局部 AMPA 受体蛋白分布密切相关。个人（UMIN000025090；研究设计：非随机，单臂；主要结果：[ ¹¹C]术前PET测量K-2摄取，术后生化检查AMPA受体蛋白密度；次要结果：PET扫描后7天的不良事件；该试验达到了预先设定的终点）。因此，[ ¹¹ C]K-2 是一种有效的 AMPA 受体 PET 示踪剂，可能提供一种工具来检查 AMPA 受体在神经精神疾病中的作用。