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- W22940972 abstract "305 Objectives Alzheimer’s disease (AD) is characterized by amyloid-β (Aβ) and tau protein deposits in the brain. The deposition of tau is more closely related to neuronal loss than that of Aβ. Thus, non-invasive detection of tau protein deposits would be useful to predict future cognitive decline as well as to track disease progression in AD. In this study, we performed the preclinical and clinical evaluation of the binding properties of novel 18F-labeled 2-phenylquinoline derivatives ([18F]THK-5105 and [18F]THK-5117). Methods Binding affinity of compounds to tau was determined by in vitro binding assays. Binding selectivity of compounds to tau pathology was evaluated by in vitro autoradiography of human brain sections. [18F]THK-5105 PET study was conducted in AD patients and healthy control subjects. Dynamic PET scans were performed after intravenous administration of [18F]THK-5105. Regional [18F]THK-5105 retention was compared with [11C]PiB retention. Results Both [18F]THK-5105 and [18F]THK-5117 binds with higher affinity to tau fibrils and tau-rich AD brain homogenates than previously-reported [18F]THK-523. Autoradiographic analyses showed that these radiotracers preferentially accumulate in tau-rich brain regions. Initial human PET studies comparing [18F]THK-5105 and [11C]PiB have shown a different regional brain distribution of these two radiotracers in AD patients (Figure 1). Noteworthy, [18F]THK-5105 was highly accumulated in the hippocampus of AD brain, despite no remarkable [11C]PiB retention in the same region. Conclusions These preclinical and clinical PET data suggest that [18F]THK-5105 and [18F]THK-5117 are promising candidates for PET tau imaging radiotracers. Further clinical studies are in progress to confirm these initial findings. Research Support Supported in part by the research fund from GE Healthcare, the Industrial Technology Research Grant Program of the NEDO, Health and Labor Sciences Research Grants from the Ministry of Health, Labor, and Welfare, and the ‘Japan Advanced Molecular Imaging Program (J-AMP)’ of the Ministry of Education, Culture, Sports, Science, and Technology of Japan." @default.
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- W22940972 date "2013-05-01" @default.
- W22940972 modified "2023-09-25" @default.
- W22940972 title "PET tau imaging in Alzheimer's disease using novel 18F-labeled 2-phenylquinoline derivatives" @default.
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