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A 18F-labeled BF-227 derivative as a potential radioligand for imaging dense amyloid plaques by positron emission tomography.

Abstract：

PURPOSE:The aims of this study were to evaluate the binding and pharmacokinetics of novel 18F-labeled ethenyl-benzoxazole derivatives (i.e., [18F] fluorinated amyloid imaging compound of Tohoku university ([18F]FACT)) as amyloid positron emission tomography (PET) tracers and to assess [18F]FACT efficacy in imaging of Alzheimer's disease (AD). PROCEDURES:Binding assay was conducted using synthetic amyloid-β (Aβ) fibrils, fluorescence microscopy, and autoradiogram in three postmortem AD brains. Pharmacokinetics of [18F]FACT was assessed using 12 Crj:CD-1 (ICR) mice. In vivo binding ability with brain amyloid was investigated using amyloid precursor protein (APP) transgenic mouse. Clinical PET scanning using [18F]FACT was performed in ten healthy controls and ten mild cognitive impairment and ten AD patients. RESULTS:[18F]FACT showed high binding affinity for synthetic Aβ fibrils, preferential binding to dense cored plaques in brain sections, and excellent brain uptake and rapid clearance in mice. Injection in APP mice resulted in specific in vivo labeling of amyloid deposits in the brain. PET scans of AD patients showed significantly higher [18F]FACT uptake in the neocortex compared to controls (P<0.05, Kruskal-Wallis test). CONCLUSION:[18F]FACT is a promising agent for imaging dense Aβ plaques in AD.

journal_name

Mol Imaging Biol

journal_title

Molecular imaging and biology

authors

Furumoto S,Okamura N,Furukawa K,Tashiro M,Ishikawa Y,Sugi K,Tomita N,Waragai M,Harada R,Tago T,Iwata R,Yanai K,Arai H,Kudo Y

doi

10.1007/s11307-012-0608-5

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

497-506

issue

4

eissn

1536-1632

issn

1860-2002

journal_volume

15

pub_type

杂志文章

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