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Error Analysis of Dopamine D2 Receptor Occupancy Study with Agonist Ligand [11c]MNPA

https://repo.qst.go.jp/records/69793
https://repo.qst.go.jp/records/69793
ececff14-9748-47f8-a2e6-180519beecd3
Item type 会議発表用資料 / Presentation(1)
公開日 2009-07-13
タイトル
タイトル Error Analysis of Dopamine D2 Receptor Occupancy Study with Agonist Ligand [11c]MNPA
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 Shidahara, Miho

× Shidahara, Miho

WEKO 685231

Shidahara, Miho

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Ito, Hiroshi

× Ito, Hiroshi

WEKO 685232

Ito, Hiroshi

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Otsuka, Tatsui

× Otsuka, Tatsui

WEKO 685233

Otsuka, Tatsui

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Ikoma, Youko

× Ikoma, Youko

WEKO 685234

Ikoma, Youko

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Seki, Chie

× Seki, Chie

WEKO 685235

Seki, Chie

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Kodaka, Fumitoshi

× Kodaka, Fumitoshi

WEKO 685236

Kodaka, Fumitoshi

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Arakawa, Ryosuke

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WEKO 685237

Arakawa, Ryosuke

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Takano, Harumasa

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WEKO 685238

Takano, Harumasa

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Takahashi, Hidehiko

× Takahashi, Hidehiko

WEKO 685239

Takahashi, Hidehiko

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Kimura, Yuichi

× Kimura, Yuichi

WEKO 685240

Kimura, Yuichi

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Kanno, Iwao

× Kanno, Iwao

WEKO 685241

Kanno, Iwao

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Suhara, Tetsuya

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WEKO 685242

Suhara, Tetsuya

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志田原 美保

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WEKO 685243

en 志田原 美保

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伊藤 浩

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WEKO 685244

en 伊藤 浩

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大塚 達以

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WEKO 685245

en 大塚 達以

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生駒 洋子

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WEKO 685246

en 生駒 洋子

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関 千江

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WEKO 685247

en 関 千江

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小高 文聰

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WEKO 685248

en 小高 文聰

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荒川 亮介

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WEKO 685249

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高野 晴成

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WEKO 685250

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高橋 英彦

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WEKO 685251

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木村 裕一

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WEKO 685252

en 木村 裕一

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菅野 巖

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WEKO 685253

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須原 哲也

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WEKO 685254

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抄録
内容記述タイプ Abstract
内容記述 Objectives: Occupancy of dopamine D2 receptors by antipsychotic drugs can be estimated from reduction in the observed binding potential (BPND). Because BPND varies widely in occupancy studies, accuracy of the measurement of wide range BPND should be confirmed. The purpose of this study is to investigate errors in quantitative analysis for estimating dopamine D2 receptor occupancy by antipsychotics with agonist ligand [11C]MNPA which has high affinity and selectivity to dopamine D2 receptors1.
\nMethods: Simulated TACs of [11C]MNPA with several noise levels were generated to investigate the bias and variation of parameter estimates caused by the statistical noise for non-linear least square (NLS) fitting and a simplified reference tissue model (SRTM) methods. A dynamic tracer concentrations was consisted of three target conditions (K1=0.44, k2=0.067, k3=0.02, 0.1 or 0.2, k4=0.18), and a reference (K1=0.44, k2=0.067) with a dynamic frame (20sec * 9, 1min * 5, 2min * 4, 4min * 11, 5min * 6, totally 90min) and a measured input function from human study1. Three true BPND values were assumed; 1.111 (baseline), 0.556 (occupancy = 50%) and 0.111 (90%). Then Gaussian noise was added at the noise level 1%, 3%, 5%, 7% and 10%, and five hundred noisy data sets were generated for each2. The reliability of BPND estimated by NLS and a SRTM and the calculated occupancy, dependency of scan durations (32, 44, 60, 75 and 90min) for SRTM were investigated.
\nResults: For NLS and SRTM methods, the bias of estimated BPND values became larger as the noise level increased and these bias of BPND were larger than those of occupancy (Fig. 1A and 1B). In the case of small BPND, the bias became larger. For SRTM method, reliable and unbiased occupancy estimates of [11C]MNPA could be obtained by 60 min with the relative standard deviation remaining less than 10%. However, shorten scan duration depredate the quantification of very small binding potential (Fig1C).
\nConclusions: Dopamine D2 receptor occupancy by antipsychotics can be estimated precisely by SRTM method with an optimal scan duration with [11C]MNPA.
\nReference:
[1] Otsuka T, 2008, Neuroimage, 41, suppl. 2, T134.
[2] Ikoma Y, 2008, Neuroimage, 47, 43-50.
[pic_01]
Fig. 1 (A) Noise level dependency: Bias of BP and Occupancy estimated by NLS, (B) estimated by SRTM, (C) Scan Duration Dependency: Bias of BP and Occupancy at a 3% noise level estimated by SRTM.
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'09 & BrainPET'09
発表年月日
日付 2009-07-03
日付タイプ Issued
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