WEKO3
アイテム
Development of an In Vivo Method to Estimate Effective Drug Doses and Quantify Fatty Acid Amide Hydrolase in Rodent Brain using Positron Emission Tomography Tracer N-(3,4-dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[11C]methylphenyl)thiazol-2-yl]-1-carboxamide ([11C]DFMC)
https://repo.qst.go.jp/records/79840
https://repo.qst.go.jp/records/798404bcd262a-79a8-4ddb-9af6-1675fb002054
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2020-04-10 | |||||
| タイトル | ||||||
| タイトル | Development of an In Vivo Method to Estimate Effective Drug Doses and Quantify Fatty Acid Amide Hydrolase in Rodent Brain using Positron Emission Tomography Tracer N-(3,4-dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[11C]methylphenyl)thiazol-2-yl]-1-carboxamide ([11C]DFMC) | |||||
| 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 |
Yamasaki, Tomoteru
× Yamasaki, Tomoteru× Ohya, Tomoyuki× Mori, Wakana× Zhang, Yiding× Wakizaka, Hidekatsu× Nengaki, Nobuki× Fujinaga, Masayuki× Kikuchi, Tatsuya× Ming-Rong, Zhang× Tomoteru, Yamasaki× Tomoyuki, Ohya× Wakana, Mori× Zhang, Yiding× Hidekatsu, Wakizaka× Nobuki, Nengaki× Masayuki, Fujinaga× Tatsuya, Kikuchi× Zhang, Ming-Rong |
|||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Fatty acid amide hydrolase (FAAH) is a key enzyme in the endocannabinoid system. N-(3,4-Dimethylisoxazol-5-yl)piperazine-4-[4-(2-fluoro-4-[11C]methylphenyl)thiazol-2-yl]-1-carboxamide ([11C]DFMC) was developed as an irreversible-type positron emission tomography (PET) ligand for FAAH. Here, we attempted to noninvasively estimate rate constant k3 as a direct index for FAAH in the rat brain. First, the two-tissue compartment model analysis including three parameters (K1–k3, 2TCMi) in PET study with [11C]DFMC was conducted, which provided 0.21 ± 0.04 mL·cm−3·min−1 of the net uptake value (Ki), an indirect index for FAAH, in the FAAH-richest region (the cingulate cortex). Subsequently, to noninvasively estimate Ki value, the reference model analysis (Patlak Reference, PGAREF) was tried using a time-activity curve of the spinal cord. In that result, the noninvasive Ki value (KREF) was concisely estimated with high correlation (r > 0.95) to Ki values based on 2TCMi. Using estimated KREF value, we tried to obtain calculated-k3 based on previously defined equations. The caluculated-k3 was successfully estimated with high correlation (r = 0.95) to direct k3 in 2TCMi. Finally, the dose relationship study using calculated-k3 demonstrated that in vivo ED50 value of URB597, a major inhibitor of FAAH, was 66.4 µg/kg in rat brain. In conclusion, we proposed the calculated-k3 as an alternative index corresponding to regional FAAH concentrations and suggested that PET with [11C]DFMC enables occupancy study for new pharmaceuticals targeting FAAH. | |||||
| 書誌情報 |
The Journal of Pharmacology and Experimental Therapeutics 巻 373, 号 3, p. 353-360, 発行日 2020-04 |
|||||
| 出版者 | ||||||
| 出版者 | ASPET | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0022-3565 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1124/jpet.119.263772 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://pubmed.ncbi.nlm.nih.gov/32241809/ | |||||
