論文 - 詳細
| RRC ID | 42775 |
|---|---|
| 著者 | Tanaka M, Fujisaki Y, Kawamura K, Ishiwata K, Qinggeletu, Yamamoto F, Mukai T, Maeda M. |
| タイトル | Radiosynthesis and evaluation of 11C-labeled diaryl-substituted imidazole and indole derivatives for mapping cyclooxygenase-2. |
| ジャーナル | Biol Pharm Bull |
| Abstract |
11C-labeled analogs of 4-chloro-5-(3-fluoro-4-methoxyphenyl)-1-(4-methylsulfonylphenyl)imidazole ([11C]1), 4-[4-chloro-5-(3-fluoro-4-methoxyphenyl)imidazol-1-yl]benzenesulfonamide ([11C]2) and 2-(4-aminosulfonylphenyl)-3-(4-methoxyphenyl)indole ([11C]3), which have been shown to have excellent potency and high selectivity for cyclooxygenase isoform 2 (COX-2) inhibiting activity, were prepared and evaluated in rats as potential radiopharmaceuticals for imaging the COX-2 enzyme by positron emission tomography. These 11C-labeled COX-2 inhibitors were synthesized in high radiochemical yields by O-[11C]methylation of phenolic precursors with [11C]methyl triflate in acetone containing NaOH as a base. In vivo evaluation in rats bearing AH109A hepatoma showed no specific binding of any tracer to COX-2 in any tissue such as the brain, heart, lung, kidney, and AH109A hepatoma. In ex vivo autoradiography, [11C]1 showed regionally different distribution in the brain, while [11C]2 and [11C]3 were not substantially taken up by the brain. In in vitro monolayer efflux assays, compound 3 was found to be a substrate for the P-glycoprotein (P-gp) efflux pump, but pretreatment of rats with the potent P-gp inhibitor, cyclosporine A, did not have any significant influence on the cerebral uptake of [11C]3. These results indicate that all three tracers were not suitable for in vivo imaging of COX-2. There seem to be some obstacles to finding a useful candidate for in vivo imaging application of COX-2 selective inhibitors only by standard consideration of in vitro affinity and selectivity, and the lipophilicity of the compound. |
| 巻・号 | 29(10) |
| ページ | 2087-94 |
| 公開日 | 2006-10-1 |
| DOI | 10.1248/bpb.29.2087 |
| PII | JST.JSTAGE/bpb/29.2087 |
| PMID | 17015956 |
| MeSH | ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology Animals Autoradiography Carbon Radioisotopes* Cyclooxygenase 2 / analysis* Cyclooxygenase 2 Inhibitors / metabolism* Imidazoles / metabolism Indoles / metabolism Isotope Labeling* Male Radiopharmaceuticals* / metabolism Rats Tissue Distribution |
| IF | 1.863 |
| 引用数 | 23 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | LLC-GA5-CoL300(RCB0872) |