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A comparison of the high-affinity peripheral benzodiazepine receptor ligands DAA1106and(R)-PK11195 in rat models of neuroinflammation:implications for PET imaging of microglial activation
https://repo.qst.go.jp/records/45064
https://repo.qst.go.jp/records/4506497b10186-1553-4a77-b55a-8261c77c1cdb
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2008-01-07 | |||||
タイトル | ||||||
タイトル | A comparison of the high-affinity peripheral benzodiazepine receptor ligands DAA1106and(R)-PK11195 in rat models of neuroinflammation:implications for PET imaging of microglial activation | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Venneti, Sriram
× Venneti, Sriram× Lopresti, Brian× Wang, Guoji× Slagel, Susan× Scott, Mason N.× Mathis, Chester× Fischer, Michelle× Larsen, Niccole× Smith, Amanda× Hastings, Teresa× Suhara, Tetsuya× Higuchi, Makoto× Wiley, Clayton× 須原 哲也× 樋口 真人 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Activated microglia are an important feature of many neurological diseases and can be imaged in vivo using 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK11195), a ligand that binds the peripheral benzodiazepine receptor (PBR). N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl) acetamide (DAA1106) is a new PBR-specific ligand that has been reported to bind to PBR with higher affinity compared with PK11195. We hypothesized that this high-affinity binding of DAA1106 to PBR will enable better delineation of microglia in vivo using positron emission tomography. [3H]DAA1106 showed higher binding affinity compared with [3H](R)-PK11195 in brain tissue derived from normal rats and the rats injected intrastriatally with 6-hydroxydopamine or lipopolysaccharide at the site of the lesion. Immunohistochemistry combined with autoradiography in brain tissues as well as correlation analyses showed that increased [3H]DAA1106 binding corresponded mainly to activated microglia. Finally, ex vivo autoradiography and positron emission tomography imaging in vivo showed greater retention of [11C]DAA1106 compared with [11C](R)-PK11195 in animals injected with either lipopolysaccaride or 6-hydroxydopamine at the site of lesion. These results indicate that DAA1106 binds with higher affinity to microglia in rat models of neuroinflammation when compared with PK11195, suggesting that [11C]DAA1106 may represent a significant improvement over [11C](R)-PK11195 for in vivo imaging of activated microglia in human neuroinflammatory disorders. | |||||
書誌情報 |
Journal of Neurochemistry 巻 102, 号 6, p. 2118-2131, 発行日 2007-09 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0022-3042 |