期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 617, 期 1-3, 页码 54-58出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2009.06.042
关键词
BF227; alpha-synuclein; Positron emission tomography; Dementia with Lewy bodies; A beta (amyloid-beta); Imaging
资金
- National Health and Medical Research Council
- Ministry of Health, Labour and Welfare, Japan
- NHMRC
Amyloid-beta (A beta) plaques are a pathological hallmark of Alzheimer's disease and a current target for positron emission tomography (PET) imaging agents. Whilst [C-11]-PiB is currently the most widely used PET ligand in clinic, a novel family of benzoxazole compounds have shown promise as A beta imaging agents; particularly BF227. We characterised the in vitro binding of [F-18]-BF227 toward alpha-synuclein to address its selectivity for A beta pathology, to establish whether [F-18]-BF227 binds to alpha-synuclein/Lewy bodies, in addition to A beta plaques. In vitro [F-18]-BF227 saturation studies were conducted with 200 nM alpha-synuclein or A beta(1-42) fibrils or 100 mu g of Alzheimer's disease, pure dementia with Lewy bodies or control brain homogenates. Non-specific binding was established with PiB (1 mu M). In vitro binding studies indicated that [F-18]-BF227 binds with high affinity to two binding sites on A beta(1-42) fibrils (K-D1 = 1.31 and K-D2 = 80 nM, respectively) and to one class of binding sites on alpha-synuclein fibrils (K-D = 9.63nM). [F-18]-BF227 bound to A beta-containing Alzheimer's disease brain (K-D = 25 +/- 0.5 nM), but failed to bind to A beta-free dementia with Lewy bodies or age-matched control homogenates. Moreover, BF227 labelled both A beta plaques and Lewy bodies in immunohistochemical/fluorescence analysis of human Alzheimer's disease and Parkinson's disease brain sections, respectively. This study suggests that [F-18]-BF227 is not A beta-selective. Evaluation of BF227 as a potential biomarker for Parkinson's disease is warranted. (C) 2009 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据