[(18)F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease - PubMed (original) (raw)

doi: 10.1016/j.jalz.2012.11.008. Epub 2013 Feb 12.

Janna Arteaga, Gang Chen, Umesh Gangadharmath, Luis F Gomez, Dhanalakshmi Kasi, Chung Lam, Qianwa Liang, Changhui Liu, Vani P Mocharla, Fanrong Mu, Anjana Sinha, Helen Su, A Katrin Szardenings, Joseph C Walsh, Eric Wang, Chul Yu, Wei Zhang, Tieming Zhao, Hartmuth C Kolb

Affiliations

[(18)F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease

Chun-Fang Xia et al. Alzheimers Dement. 2013 Nov.

Abstract

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 Aβ rather than synthetic tau aggregates or Aβ fibrils generated in vitro to measure the affinity and selectivity of [(18)F]T807 to tau and Aβ. Brain uptake and biodistribution of [(18)F]T807 in mice were also tested.

Results: In vitro autoradiography results show that [(18)F]T807 exhibits strong binding to PHF-tau-positive human brain sections. A dissociation constant (Kd) of [(18)F]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 Aβ on adjacent sections demonstrated that [(18)F]T807 binding colocalized with immunoreactive PHF-tau pathology, but did not highlight Aβ plaques. In vivo studies in mice demonstrated that [(18)F]T807 was able to cross the blood-brain barrier and washed out quickly.

Conclusions: [(18)F]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.

Keywords: Alzheimer’s disease; Amyloid β; Autoradiography; Imaging; Tau; [(18)F]T807.

Copyright © 2013 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

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