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01-08-2013 | Research Article

A ¹⁸F-Labeled BF-227 Derivative as a Potential Radioligand for Imaging Dense Amyloid Plaques by Positron Emission Tomography

Authors: 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

Published in: Molecular Imaging and Biology | Issue 4/2013

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.

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Title: A 18F-Labeled BF-227 Derivative as a Potential Radioligand for Imaging Dense Amyloid Plaques by Positron Emission Tomography
Authors: 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
Publication date: 01-08-2013
Publisher: Springer US
Published in: Molecular Imaging and Biology / Issue 4/2013
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-012-0608-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

A ¹⁸F-Labeled BF-227 Derivative as a Potential Radioligand for Imaging Dense Amyloid Plaques by Positron Emission Tomography

Abstract

Purpose

Procedures

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusion

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