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  • 08월 28일 16시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능

The development of PET imaging agents for diagnosis of Alzheimer’s disease

2008년 8월 12일 11시 05분 19초
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목 14시 : 00분
의약화학 - Recent Drug Development of Neurodegenerative Disease
저자 및
한국과학기술연구원 케모인포매틱스연구단, Korea
Alzheimer’s disease (AD) is pathologically characterized by the accumulation of beta-amyloid plaques and neurofibrillary tangles in the brain. Such plaques can be excellent targets for in vivo brain imaging of AD patients as an early diagnosis of AD. Development of imaging probes for direct marking of beta-amyloid aggregates in the living brain is a highly active research area in recent years. For instance, Pittsburgh compound B (PIB), a derivative of Thioflavin T with high binding affinity to beta-amyloid fibrils, is the most common imaging agent used in investigational studies of AD via positron emission tomography (PET). In this study a novel series of 2,3-dihydroisoindol-1-one and 1,3-dione derivatives for beta-amyloid specific binding agents is described. Thirty cold compounds for a binding study, were synthesized and evaluated by a competitive binding assay with [125I]TZDM against beta-amyloid aggregates. Most of the synthesized compounds displayed higher binding affinities, with Ki value in the subnanomolar range (0.16-1.05 nM), than PIB (Ki = 0.77 nM). Novel synthesized [11C]- and [18F]-labeled isoindole derivatives were evaluated as potential beta-amyloid imaging agents based on their in vivo pharmacokinetic studies using micro-PET. Most of the radio-labeled compounds showed high brain uptake and excellent clearance in normal mice. The results suggest that these [11C]- and [18F]-labeled compounds are potential PET imaging probes for studying accumulation of beta-amyloid fibrils in the brains of AD patients.