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Nitroxyl radicals for labeling of conventional therapeutics and noninvasive magnetic resonance imaging of their permeability for blood-brain barrier: Relationship between structure, blood clearance, and MRI signal dynamic in the brain
https://repo.qst.go.jp/records/48486
https://repo.qst.go.jp/records/48486deda2b44-84eb-4148-a169-43d862b1e189
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2018-02-13 | |||||
| タイトル | ||||||
| タイトル | Nitroxyl radicals for labeling of conventional therapeutics and noninvasive magnetic resonance imaging of their permeability for blood-brain barrier: Relationship between structure, blood clearance, and MRI signal dynamic in the brain | |||||
| 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 |
Zhelev, Zhivko
× Zhelev, Zhivko× Bakalova-Zheleva, Rumiana× Aoki, Ichio× Matsumoto, Kenichiro× Veselina, Gadjeva× Anzai, Kazunori× Kanno, Iwao× Ｚｈｅｌｅｖ Ｚｈｉｖｋｏ× バカロバ ルミアナ× 青木 伊知男× 松本 謙一郎× 安西 和紀× 菅野 巖 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | The present study describes a novel nonradioactive methodology for in vivo noninvasive, real-time imaging of blood−brain barrier (BBB) permeability for conventional drugs, using nitroxyl radicals as spin-labels and magnetic resonance imaging (MRI). Two TEMPO-labeled analogues (SLENU and SLCNUgly) of the anticancer drug lomustine [1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea] were synthesized, using a substitution of the cyclohexyl part with nitroxyl radical. Nonmodified nitroxyl radical TEMPOL was used for comparison. The nitroxyl derivatives were injected intravenously in healthy mice via the tail vein, and MR imaging of the brain was performed on a 7.0 T MRI. The MRI signal dynamic of SLENU and SLCNUgly followed the same kinetics as nonmodified TEMPO radical. SLENU and SLCNUgly were rapidly transported and randomly distributed in the brain tissue, which indicated that the exchange of cyclohexyl part of lomustine with TEMPO radical did not suppress the permeability of the anticancer drug for BBB. The selected nitroxyl derivatives possessed different hydrophobicity, cell permeabilization ability, and blood clearance. Based on these differences, we investigated the relationship between the structure of nitroxyl derivatives, their half-life in the circulation, and their MRI signal dynamic in the brain. This information was important for estimation of the merits and demerits of the described methodology and finding pathways for overcoming the restrictions. | |||||
| 書誌情報 |
Molecular Pharmaceutics 巻 6, 号 2, p. 504-512, 発行日 2009-04 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1543-8384 | |||||
