Quantitative analysis of donepezil binding to acetylcholinesterase using positron emission tomography and [5-11C-methoxy]donepezil

Kotaro Hiraoka, Nobuyuki Okamura, Yoshihito Funaki, Shoichi Watanuki, Manabu Tashiro, Motohisa Kato, Akiko Hayashi, Yoshiyuki Hosokai, Hiroshi Yamasaki, Toshikatsu Fujii, Etsuro Mori, Kazuhiko Yanai, Hiroshi Watabe

研究成果: Article査読

18 被引用数 (Scopus)

抄録

The aim of this study was to establish kinetic analysis of [5-11C-methoxy]donepezil ([11C]donepezil), which was developed for the in-vivo visualization of donepezil binding to acetylcholinesterase (AChE) using positron emission tomography (PET). Donepezil is an AChE inhibitor that is widely prescribed to ameliorate the cognitive impairment of patients with dementia. Six healthy subjects took part in a dynamic study involving a 60-min PET scan after intravenous injection of [11C]donepezil. The total distribution volume (tDV) of [11C]donepezil was quantified by compartmental kinetic analysis and Logan graphical analysis. A one-tissue compartment model (1TCM) and a two-tissue compartment model (2TCM) were applied in the kinetic analysis. Goodness of fit was assessed with χ2 criterion and Akaike's Information Criterion (AIC). Compared with a 1TCM, goodness of fit was significantly improved by a 2TCM. The tDVs provided by Logan graphical analysis were slightly lower than those provided by a 2TCM. The rank order of the mean tDVs in 10 regions was in line with the AChE activity reported in a previous post-mortem study. Logan graphical analysis generated voxel-wise images of tDV, revealing the overall distribution pattern of AChE in individual brains. Significant correlation was observed between tDVs calculated with and without metabolite correction for plasma time-activity curves, indicating that metabolite correction could be omitted. In conclusion, this method enables quantitative analysis of AChE and direct investigation of the pharmacokinetics of donepezil in the human brain.

本文言語English
ページ(範囲)616-623
ページ数8
ジャーナルNeuroImage
46
3
DOI
出版ステータスPublished - 2009 7 1

ASJC Scopus subject areas

  • Neurology
  • Cognitive Neuroscience

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