| Autor: |
Gengyang, Yuan, Maeva, Dhaynaut, Yu, Lan, Nicolas J, Guehl, Dalena, Huynh, Suhasini M, Iyengar, Sepideh, Afshar, Manish Kumar, Jain, Julie E, Pickett, Hye Jin, Kang, Hao, Wang, Sung-Hyun, Moon, Mary Jo, Ondrechen, Changning, Wang, Timothy M, Shoup, Georges, El Fakhri, Marc D, Normandin, Anna-Liisa, Brownell |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
J Med Chem |
| ISSN: |
1520-4804 |
| Popis: |
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-[(11)C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]-pyridine-7-carboxamide ([(11)C]13, [(11)C]mG2N001), a potent negative allosteric modulator (NAM), was developed to support this endeavor. [(11)C]13 was synthesized via the O-[(11)C]methylation of phenol 24 with a high molar activity of 212 ± 76 GBq/μmol (n = 5) and excellent radiochemical purity (>99%). PET imaging of [(11)C]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, [(11)C]13 selectively accumulated in mGluR2-rich regions and resulted in high-contrast brain images. Therefore, [(11)C]13 is a potential candidate for translational PET imaging of the mGluR2 function. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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