Metabotropic glutamate receptor 2 (mGluR2) is a therapeutic target for several neuropsychiatric disorders. An mGluR2 function in etiology could be unveiled by positron emission tomography (PET). In this regard, 5-(2-fluoro-4-[¹¹C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridine-7-carboxamide ([¹¹C]13, [¹¹C]mG2N001), a potent negative allosteric modulator (NAM), was developed to support this endeavor. [¹¹C]13 was synthesized via the O-[¹¹C]methylation of phenol 24 with a high molar activity of 212 ± 76 GBq/μmol (n = 5) and excellent radiochemical purity (>99%). PET imaging of [¹¹C]13 in rats demonstrated its superior brain heterogeneity and reduced accumulation with pretreatment of mGluR2 NAMs, VU6001966 (9) and MNI-137 (26), the extent of which revealed a time-dependent drug effect of the blocking agents. In a nonhuman primate, [¹¹C]13 selectively accumulated in mGluR2-rich regions and resulted in high-contrast brain images. Therefore, [¹¹C]13 is a potential candidate for translational PET imaging of the mGluR2 function.

中文翻译：

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5-(2-Fluoro-4-[11C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridine-7-carboxamide 的合成和表征作为 PET 成像代谢型谷氨酸受体 2 的配体

代谢型谷氨酸受体 2 (mGluR2) 是多种神经精神疾病的治疗靶点。正电子发射断层扫描 (PET) 可以揭示 mGluR2 在病因学中的功能。在这方面，5-(2-fluoro-4-[ ¹¹ C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro-2 H -pyrano[2,3- b ]pyridine-7-carboxamide ([ ¹¹ C] 13 , [ ¹¹ C]mG2N001) 是一种有效的负变构调节剂 (NAM)，旨在支持这一努力。[ ¹¹ C] 13是通过苯酚24的O -[ ¹¹ C] 甲基化合成的，具有 212 ± 76 GBq/μmol 的高摩尔活性（n= 5) 和出色的放射化学纯度 (>99%)。^{[ 11} C] 13在大鼠中的 PET 成像显示其优越的脑异质性并通过 mGluR2 NAM、VU6001966 ( 9 ) 和 MNI-137 ( 26 )的预处理减少积聚，其程度揭示了阻断的时间依赖性药物效应代理商。在非人类灵长类动物中，[ ¹¹ C] 13选择性地聚集在富含 mGluR2 的区域，并产生高对比度的大脑图像。因此，[ ¹¹ C] 13是 mGluR2 功能的平移 PET 成像的潜在候选者。