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Correction for Radiolabeled O-Methyl Metabolite in Human Brain
https://repo.qst.go.jp/records/72104
https://repo.qst.go.jp/records/7210486c52139-e43b-4d53-9636-3dbcf37b24d6
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2016-12-22 | |||||
| タイトル | ||||||
| タイトル | Correction for Radiolabeled O-Methyl Metabolite in Human 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_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 |
Matsubara, Keisuke
× Matsubara, Keisuke× Ito, Hiroshi× Ikoma, Yoko× Okada, Maki× Masanobu, Ibaraki× Nakamura, Kazuhiro× Yamaguchi, Hiroshi× Suhara, Tetsuya× Kinoshita, Toshibumi× 松原 佳亮× 伊藤 浩× 生駒 洋子× 岡田 真希× 茨木 正信× 中村 和浩× 山口 博司× 須原 哲也 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Objectives: Dopamine synthesis rate, one of the presynaptic functions of the central dopaminergic system, can be measured by positron emission tomography (PET) measurement with L-[β-11C]DOPA [1]. The radiolabeled O-methyl metabolite of L-[β-11C]DOPA in peripheral organ, L-[β-11 C]O-methyl-DOPA (L-[β-11C]OMD), suggested to penetrate the blood-brain barrier (BBB). Thus, L-[β- 11C]OMD may affect tissue radioactivity measured by PET and the endogenous dopamine synthesis rate estimated by kinetic analyses. However, the influence of L-[β-11C]OMD in the living tissue for the kinetic analyses has not been investigated in detail. In the present study, to evaluate the influence of L-[β-11C]OMD on the tissue time-activity curve (TAC) with L-[β-11C]DOPA PET, the metabolite correction was applied to tissue TACs acquired from healthy volunteers. Methods: The metabolite correction method proposed by Kumakura et al. in [18F]FDOPA PET study [2] was employed. In this method, component for O-methyl metabolite in the tissue TAC is estimated by compartmental analysis with two kinds of arterial input function for L-[β-11C]DOPA and L-[β-11 C]OMD, and TAC in occipital cortex as a reference region with no irreversible binding. TAC in each brain region for L-[β-11C]DOPA PET studies with ten healthy volunteers [1] was corrected by using the estimated L-[β-11C]OMD TAC. This method assumes the distribution of O-methyl metabolite is uniform around the brain [3]. The endogenous dopamine synthesis rate (Ki) was estimated by Gjedde-Patlak plot analysis with the arterial input function and the metabolite-corrected TAC. The Ki was also estimated from the non-corrected TAC. For comparison to conventional analysis, relative influx constant (kref) was also estimated by Gjedde-Patlak plot analysis using TAC in occipital cortex, regarded as reference tissue input function. Data of 29 – 64 min and 29 – 89 min were used for linear regression in Gjedde-Patlak plot analysis. Results: Calculated OMD component had only a marginal effect on tissue TAC (fraction of area under curve (AUC) of L-[β-11C]OMD TAC in putaminal TAC: 9.4 ± 2.1 %). Ki with no metabolite corrected TAC correlated significantly to Ki with the metabolite correction (p < 0.001, r = 0.99 (29 – 64 min), p < 0.001, r = 0.99 (29 – 89 min)), and Ki were overestimated in all brain regions with no metabolite correction, see Figure A. kref also correlated to Ki with the metabolite correction, as shown in Figure B (p < 0.001, r = 0.99 (29 – 64 min), p < 0.001, r = 0.99 (29 – 89 min)). Conclusion: The results suggest that the influence of the O-methyl metabolite L-[β-11C]OMD to tissue TAC and kinetic parameters in L-[β-11C]DOPA PET is marginal. This finding is accounted for by low fraction of L-[β-11C]OMD in plasma in case of L-[β-11C]DOPA, in contrast with high fraction of O-methyl metabolite for [18F]FDOPA. The results also suggest the net endogenous dopamine synthesis rate can be determined without the metabolite correction in case of L-[β-11C]DOPA, not same as [18 F]FDOPA. Reference [1] Ito H., et al., 2006, Nucl. Med. Commun. 27, 723-731 [2] Kumakura Y., et al., 2005, J. Cereb. Blood Flow Metab. 25, 807-819 [3] Doudet D.J., et al., 1991, J. Cereb. Blood Flow Metab. 11, 726-734 Note - image will be printed in black & white |
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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 | The Ninth International Symposium on Functional Neuroreceptor Mapping of the Living Brain | |||||
| 発表年月日 | ||||||
| 日付 | 2012-08-10 | |||||
| 日付タイプ | Issued | |||||
