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Quantitative analysis of amyloid deposition in alzheimer disease using PET and [C-11]AZD2184
https://repo.qst.go.jp/records/71608
https://repo.qst.go.jp/records/7160820a99c78-b973-43d1-a47e-30ce8d3157d7
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2015-04-20 | |||||
| タイトル | ||||||
| タイトル | Quantitative analysis of amyloid deposition in alzheimer disease using PET and [C-11]AZD2184 | |||||
| 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_c94f | |||||
| 資源タイプ | conference object | |||||
| 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 |
Ito, Hiroshi
× Ito, Hiroshi× Shimada, Hitoshi× Shinotoh, Hitoshi× Takano, Harumasa× Kodaka, Fumitoshi× Kimura, Yasuyuki× Fujiwara, Hironobu× Ikoma, Youko× Seki, Chie× Higuchi, Makoto× Fukumura, Toshimitsu× Lindstrom, Boo Eva× Farde, Lars× Suhara, Tetsuya× 伊藤 浩× 島田 斉× 篠遠 仁× 高野 晴成× 小高 文聰× 木村 泰之× 藤原 広臨× 生駒 洋子× 関 千江× 樋口 真人× 福村 利光× 須原 哲也 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Objectives: Characteristic neuropathologic changes in Alzheimer disease (AD) are amyloid-beta deposits and neurofibrillary tangles. Carbon-11-labeled 5-(6-{[tert-butyl (dimethyl) silyl]oxy}-1,3-benzothiazol-2-yl) pyridin-2-amine ([C-11]AZD2184) is a more recently developed radiotracer for amyloid-beta deposits. [C-11]AZD2184 has high affinity in vitro for amyloid fibrils (dissociation constant, KD: 8.4 +- 1.0 nM) [1]. After intravenous injection of [C-11]AZD2184, there was rapid uptake of radioactivity in the brain followed by rapid washout in control subjects as well as in AD patients in an initial human study [2]. In this study, [C-11]AZD2184 binding in control subjects and AD patients was examined in more detail by compartment model analysis using a metabolite-corrected arterial input function. The accuracy of simplified quantitative methods employing a reference brain region was also evaluated. Methods: After intravenous bolus injection of [C-11]AZD2184, a dynamic PET scan was performed for 90 minutes in 6 control subjects and 8 AD patients. To obtain the arterial input function, arterial blood sampling and HPLC analysis were performed. To interpret the kinetic behaviour of [C-11]AZD2184, the standard two-tissue compartment model with four first-order rate constants (K1, k2, k3 and k4) was employed. The rate constants were estimated by non-linear curve fitting which was performed in a least-squares sense to the regional time-activity curves. Since the cerebellum can be used as a reference brain region, the total distribution volume ratio (DVR) of brain regions to cerebellum. In addition, the standardized uptake value ratio (SUVR) of brain regions to cerebellum obtained from integrated time-activity curves with integration intervals of 20-40 min, 40-60 min, and 60-90 min were calculated as the indicator of amyloid-beta deposits. Results: Time-activity curves in all brain regions could be described using the standard two-tissue compartment model. Binding potentials (BPND, equal to k3/k4) in cerebral cortical regions were higher in AD patients than in control subjects (AD patients: 2.0-2.3, control subjects: 1.0-1.1). Although there was no conspicuous accumulation of radioactivity in white matter as compared with other amyloid radioligands, BPND values were identified by compartment model analysis of the centrum semiovale for both control subjects and AD patients (about 1.7), suggesting binding to myelin. SUVR with each integration interval was in good agreement with DVR (AD patients: 1.8-2.6, control subjects: 1.0-1.2). Conclusions: It has been estimated that regions-of-interest defined for the cerebral cortex contain about 60% of gray matter and 30% of white matter [3]. This tissue heterogeneity may be one reason for the BPND values of [C-11]AZD2184 in cerebral cortical regions for control subjects. Although the white matter binding of [C-11]AZD2184 may have some effect on cortical uptake, it can be concluded that the kinetic behavior of [C-11]AZD2184 is suitable for quantitative analysis. SUVR can be used as a validated measure of [C-11]AZD2184 binding in clinical investigations without arterial input function. References: [1] Johnson AE, et al. J Neurochem 2009; 108: 1177-1186. [2] Nyberg S, et al. Eur J Nucl Med Mol Imaging 2009; 36: 1859-1863. [3] Ito H, et al. Neuroimage 2008; 39: 555-565. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Brain & BrainPET 2013 | |||||
| 発表年月日 | ||||||
| 日付 | 2013-05-23 | |||||
| 日付タイプ | Issued | |||||
