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[ 18 F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease
Author(s) -
Xia ChunFang,
Arteaga Janna,
Chen Gang,
Gangadharmath Umesh,
Gomez Luis F.,
Kasi Dhanalakshmi,
Lam Chung,
Liang Qianwa,
Liu Changhui,
Mocharla Vani P.,
Mu Fanrong,
Sinha Anjana,
Su Helen,
Szardenings A. Katrin,
Walsh Joseph C.,
Wang Eric,
Yu Chul,
Zhang Wei,
Zhao Tieming,
Kolb Hartmuth C.
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.11.008
Subject(s) - biodistribution , positron emission tomography , in vivo , human brain , chemistry , ex vivo , in vitro , pathology , nuclear medicine , neuroscience , medicine , biology , biochemistry , microbiology and biotechnology
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 ( K d ) 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.