期刊
ALZHEIMERS & DEMENTIA
卷 9, 期 6, 页码 666-676出版社
WILEY
DOI: 10.1016/j.jalz.2012.11.008
关键词
[F-18]T807; Tau; Amyloid beta; Alzheimer's disease; Imaging; Autoradiography
Objective: We wished to develop a highly selective positron emission tomography (PET) imaging agent targeting PHF-tau in human Alzheimer's disease (AD) brains. Methods: To screen potential tau binders, human AD brain sections were used as a source of native paired helical filament (PHF)-tau and A beta rather than synthetic tau aggregates or A beta fibrils generated in vitro to measure the affinity and selectivity of [F-18]T807 to tau and All Brain uptake and biodistribution of [F-18]T807 in mice were also tested. Results: In vitro autoradiography results show that [F-18]T807 exhibits strong binding to PHF-tau-positive human brain sections. A dissociation constant (K-d) of [F-18]T807 (14.6 nM) was measured using brain sections from the frontal lobe of AD patients. A comparison of autoradiography and double immunohistochemical staining of PHF-tau and A beta on adjacent sections demonstrated that [F-18]T807 binding colocalized with immunoreactive PHF-tau pathology, but did not highlight A beta plaques. In vivo studies in mice demonstrated that [F-18]T807 was able to cross the blood brain barrier and washed out quickly. Conclusions: [F-18]T807 demonstrates high affinity and selectivity to PHF-tau as well as favorable in vivo properties, making this a promising candidate as an imaging agent for AD. (C) 2013 The Alzheimer's Association. All rights reserved.
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