A novel imaging probe for in vivo detection of neuritic and diffuse amyloid plaques in the brain

Nobuyuki Okamura, Takahiro Suemoto, Tsuyoshi Shiomitsu, Masako Suzuki, Hiroshi Shimadzu, Hiroyasu Akatsu, Takayuki Yamamoto, Hiroyuki Arai, Hidetada Sasaki, Kazuhiko Yanai, Matthias Staufenbiel, Yukitsuka Kudo, Tohru Sawada

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41 Citations (Scopus)

Abstract

Extensive deposition of neuritic and diffuse amyloid plaques in the brain is a critical event for the pathogenesis of Alzheimer's disease (AD) and considered to start before the appearance of clinical symptoms. In vivo detection of these brain β-amyloid (Aβ) deposits using positron emission tomography (PET), therefore, would be a useful marker for presymptomatic detection of AD. To develop a new agent for PET probe of imaging neuritic and diffuse amyloid deposits, novel fluorescent compounds, including styryl-fluorobenzoxazole derivatives, were examined. These compounds showed a high binding affinity for both synthetic Aβ1-40 and Aβ1-42 aggregates. Some of these compounds also displayed distinct staining of neuritic and diffuse amyloid plaques in AD brain sections. A biodistribution study of styryl-fluorobenzoxazole derivatives in normal mice exhibited excellent brain uptakes (4.5-5.5% injected dose/g at 2 min postinjection). Furthermore, iv administration of BF-145, a styryl-fluorobenzoxazole derivative, demonstrated specific in vivo labeling of compact and diffuse amyloid deposits in an APP23 transgenic mouse brain, in contrast to no accumulation in a wild-type mouse brain. These findings suggest that BF-145 is a potential candidate as a probe for imaging early brain pathology in AD patients.

Original languageEnglish
Pages (from-to)247-255
Number of pages9
JournalJournal of Molecular Neuroscience
Volume24
Issue number2
DOIs
Publication statusPublished - 2004 Sep

Keywords

  • Alzheimer's disease
  • Amyloid-β protein
  • Imaging
  • Neurofibrillary tangles
  • Positron emission tomography
  • Senile plaques

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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    Okamura, N., Suemoto, T., Shiomitsu, T., Suzuki, M., Shimadzu, H., Akatsu, H., Yamamoto, T., Arai, H., Sasaki, H., Yanai, K., Staufenbiel, M., Kudo, Y., & Sawada, T. (2004). A novel imaging probe for in vivo detection of neuritic and diffuse amyloid plaques in the brain. Journal of Molecular Neuroscience, 24(2), 247-255. https://doi.org/10.1385/JMN:24:2:247