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

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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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Acknowledgments

This study was financially supported by the Special Coordination Funds for Promoting Science and Technology, the Health and Labour Sciences Research Grants for Translational research from Ministry of Health, Labour and Welfare, the Program for Promotion of Fundamental Studies in Health Science of the National Institute of Biomedical Innovation, and the Grant-in-Aid for Scientific Research (C) (20591432) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The authors appreciate the technical assistance of Dr. Shoichi Watanuki in the clinical PET studies.

Conflict of Interest

The authors declare they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan

    Shozo Furumoto, Nobuyuki Okamura, Kentaro Sugi, Ryuichi Harada & Kazuhiko Yanai

  2. Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan

    Shozo Furumoto, Yoichi Ishikawa, Tetsuro Tago & Ren Iwata

  3. Department of Geriatrics and Gerontology, Division of Brain Sciences, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan

    Katsutoshi Furukawa, Naoki Tomita, Masaaki Waragai & Hiroyuki Arai

  4. Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan

    Manabu Tashiro

  5. Clinical Research, Innovation and Education Center, Tohoku University Hospital, Sendai, Japan

    Yukitsuka Kudo

Authors
  1. Shozo Furumoto
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  2. Nobuyuki Okamura
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  3. Katsutoshi Furukawa
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  4. Manabu Tashiro
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  5. Yoichi Ishikawa
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  6. Kentaro Sugi
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  7. Naoki Tomita
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  8. Masaaki Waragai
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  9. Ryuichi Harada
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  10. Tetsuro Tago
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  11. Ren Iwata
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  12. Kazuhiko Yanai
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  13. Hiroyuki Arai
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  14. Yukitsuka Kudo
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Corresponding author

Correspondence to Nobuyuki Okamura.

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Furumoto, S., Okamura, N., Furukawa, K. et al. A 18F-Labeled BF-227 Derivative as a Potential Radioligand for Imaging Dense Amyloid Plaques by Positron Emission Tomography. Mol Imaging Biol 15, 497–506 (2013). https://doi.org/10.1007/s11307-012-0608-5

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  • DOI: https://doi.org/10.1007/s11307-012-0608-5

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