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

Shozo Furumoto, Nobuyuki Okamura, Katsutoshi Furukawa, Manabu Tashiro, Yoichi Ishikawa, Kentaro Sugi, Naoki Tomita, Masaaki Waragai, Ryuichi Harada, Tetsuro Tago, Ren Iwata, Kazuhiko Yanai, Hiroyuki Arai, Yukitsuka Kudo

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)497-506
Number of pages10
JournalMolecular Imaging and Biology
Volume15
Issue number4
DOIs
Publication statusPublished - 2013 Aug

Keywords

  • Alzheimer's disease
  • Amyloid
  • Early diagnosis
  • Positron emission tomography

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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