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- W2024694090 abstract "Alzheimer's disease (AD) is pathologically characterized by the accumulation of 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 Aβ 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 β-amyloid (Aβ) 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 fluoroisoindolone derivatives for Aβ specific binding agents is described. Cold compounds, labeled with 19F for a binding study, were synthesized and evaluated by a competitive binding assay with [125I]TZDM against Aβ(1-42) aggregates. [18F]-labeled isoindole derivatives, hot compounds, were evaluated as potential Aβ imaging agents based on their in vivo pharmacokinetic studies using micro-PET. Most of the synthesized compounds displayed higher binding affinities, with Ki value in the subnanomolar than PIB (Ki = 0.77 nM). Most of the radio-labeled compounds showed high brain uptake and excellent clearance in normal mice. Aβ fibril labeling abilities were confirmed via ex vivo staining on brain tissues of AD transgenic mice. The preliminary results suggest that these [18F]-labeled compounds are potential PET imaging probes for studying accumulation of Aβ fibrils in the brains of AD patients." @default.
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- W2024694090 date "2010-07-01" @default.
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- W2024694090 title "IC-P-088: Fluoroisoindolone Derivatives as Potential PET Imaging Agents for Detection of Beta-Amyloid Fibrils" @default.
- W2024694090 doi "https://doi.org/10.1016/j.jalz.2010.05.102" @default.
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