title: [(18)F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease.
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.
authors: Molecular Imaging Biomarker Research, Siemens Medical Solution USA, Inc, Culver City, CA, USA.
authors: Chun-Fang
authors: CF
authors: Xia
authors: Janna
authors: J
authors: Arteaga
authors: Gang
authors: G
authors: Chen
authors: Umesh
authors: U
authors: Gangadharmath
authors: Luis F
authors: LF
authors: Gomez
authors: Dhanalakshmi
authors: D
authors: Kasi
authors: Chung
authors: C
authors: Lam
authors: Qianwa
authors: Q
authors: Liang
authors: Changhui
authors: C
authors: Liu
authors: Vani P
authors: VP
authors: Mocharla
authors: Fanrong
authors: F
authors: Mu
authors: Anjana
authors: A
authors: Sinha
authors: Helen
authors: H
authors: Su
authors: A Katrin
authors: AK
authors: Szardenings
authors: Joseph C
authors: JC
authors: Walsh
authors: Eric
authors: E
authors: Wang
authors: Chul
authors: C
authors: Yu
authors: Wei
authors: W
authors: Zhang
authors: Tieming
authors: T
authors: Zhao
authors: Hartmuth C
authors: HC
authors: Kolb
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D014018:Tissue Distribution; D016875:tau Proteins / Q000737:chemistry* / Q000187:drug effects* / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D005462:Fluorine Radioisotopes; D016875:tau Proteins
keywords: Alzheimer’s disease; Amyloid β; Autoradiography; Imaging; Tau; [(18)F]T807