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

作者：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

来源：Journal of Molecular Neuroscience, 2004, 24(2): 247-255.

DOI：10.1385/JMN:24:2:247

• amyloid-beta protein
• senile plaques
• neurofibrillary tangles
• imaging
• Alzheimer's disease
• positron emission tomography

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 beta-amyloid (Abeta) 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 Abeta1-40 and Abeta1-42 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.

• 出版日期2004