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Assessment of radioligands for PET imaging of cyclooxygenase-2 in an ischemic neuronal injury model.
https://repo.qst.go.jp/records/47100
https://repo.qst.go.jp/records/47100840f4495-dc9b-4666-995b-ca887bfb0037
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2015-04-20 | |||||
タイトル | ||||||
タイトル | Assessment of radioligands for PET imaging of cyclooxygenase-2 in an ischemic neuronal injury model. | |||||
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 |
Ji, Bin
× Ji, Bin× Kumata, Katsushi× Onoe, Hirotaka× Kaneko, Hiroyuki× Zhang, Ming-Rong× Seki, Chie× Ono, Maiko× Shukuri, Miho× Tokunaga, Masaki× Minamihisamatsu, Takeharu× Suhara, Tetsuya× Higuchi, Makoto× 季 斌× 熊田 勝志× 尾上 浩隆× 金子 博之× 張 明栄× 関 千江× 小野 麻衣子× 宿里 充穂× 徳永 正希× 南久松 丈晴× 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 | Cyclooxygenase-2 (COX-2) plays crucial roles in progressive neuronal death in ischemic brain injury. In the present study, we evaluated two radiolabeled COX-2 selective inhibitors, [11C]celecoxib and [11C]rofecoxib, as positron emission tomography (PET) tracers for COX-2 imaging in normal and ischemic mouse brains. We also took advantage of our newly-generated antibody highly selective for mouse COX-2 to prove accumulation of the radioligands in regions enriched with COX-2. In vitro autoradiography demonstrated specific binding of high-concentration [11C]rofecoxib but not [11C]celecoxib to the cerebellum and brain stem of normal brains wherein COX-2 immunoreactivity in neurons was most abundantly observed. Meanwhile, both of these radioligands failed to detect COX-2 expression in PET assays despite their excellent brain permeability. Hypoperfusion-induced ischemia caused marked necrotic neuron death accompanied by gliosis and enhancement of neuronal COX-2 immunoreactivity in the hippocampus. Correspondingly, in vitro autoradiographic binding of [11C]rofecoxib was increased in the injured hippocampus compared to the uninjured contralateral region, but failed in living brains of ischemia model likewise. Our work provides the rationale for monitoring COX-2 as a biomarker reflecting ischemic brain injuries and demonstrates that [11C]rofecoxib, not [11C]celecoxib, is useful for in vitro assays of COX-2, but its affinity would be insufficient for in vivo PET visualization. | |||||
書誌情報 |
Brain research 巻 1533, p. 152-162, 発行日 2013-08 |
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出版者 | ||||||
出版者 | Elsevier | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0006-8993 | |||||
PubMed番号 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 23973859 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1016/j.brainres.2013.08.026 |