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Quantitative analysis of 11C-verapamil transfer at the human blood-brain barrier for evaluation of P-glycoprotein function
https://repo.qst.go.jp/records/47341
https://repo.qst.go.jp/records/47341d5cf0205-4f74-4f40-820e-418e396f143c
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2015-11-30 | |||||
| タイトル | ||||||
| タイトル | Quantitative analysis of 11C-verapamil transfer at the human blood-brain barrier for evaluation of P-glycoprotein function | |||||
| 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 |
Ikoma, Yoko
× Ikoma, Yoko× Takano, Akihiro× Ito, Hiroshi× Kusuhara, Hiroyuki× Sugiyama, Yuichi× Arakawa, Ryosuke× Fukumura, Toshimitsu× Nakao, Ryuji× Suzuki, Kazutoshi× Suhara, Tetsuya× 生駒 洋子× 高野 晶寛× 伊藤 浩× 楠原 洋之× 荒川 亮介× 福村 利光× 中尾 隆士× 鈴木 和年× 須原 哲也 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | P-glycoprotein in the blood–brain barrier (BBB) has been found to be associated with several types of neurologic damage. 11CVerapamil has been used for in vivo imaging of P-glycoprotein function in the BBB by PET, but metabolites in plasma complicate the quantitative analysis of human studies. In this study, we validated the quantification methods of 11C-verapamil transfer from plasma to the brain in humans. Methods: The transfer rate constant from plasma to the brain, K1, was estimated by nonlinear least squares (NLS) with a 2-input compartment model, including the permeation of the main metabolite in plasma at the BBB, and with a 1-input compartment model using only 15-min data that contained little metabolite in plasma. K1 was also estimated by graphical analysis of an integration plot that uses only early-time data, before the appearance of metabolites, and the estimated K1 was compared with that obtained by the NLS method. In the simulation study, the reliability of parameter estimates in the graphical analysis method was investigated for various values of rate constants, time ranges of parameter estimations, and noise levels. Results: 11C-Verapamil in plasma gradually converted to its metabolites, and about 45% of the radioactivity in the plasma specimen was associated with 11Cverapamil metabolites at 30 min after injection. Although K1 estimated from graphical analysis was slightly smaller than that by NLS, there was strong correlation among the K1 values obtained by these 3 methods. In the simulation study, for graphical analysis, the differences between the true and mean of K1 estimates became larger and the coefficient of variation (COV) of K1 estimates became smaller as the end time of linear regression became later. The COV of graphical analysis was almost equal to that of NLS with the 1-input compartment model. Conclusion: The transfer of 11C-verapamil from plasma to the brain was able to be quantitatively estimated by graphical analysis because this method can provide K1 from the data of the initial few minutes without considering the effect of the metabolites in plasma. | |||||
| 書誌情報 |
Journal of Nuclear Medicine 巻 47, 号 9, p. 1531-1537, 発行日 2006-09 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0161-5505 | |||||
