title: Pathological correlations of [F-18]-AV-1451 imaging in non-alzheimer tauopathies.
abstract: OBJECTIVE
  Recent studies have shown that positron emission tomography (PET) tracer AV-1451 exhibits high binding affinity for paired helical filament (PHF)-tau pathology in Alzheimer's brains. However, the ability of this ligand to bind to tau lesions in other tauopathies remains controversial. Our goal was to examine the correlation of in vivo and postmortem AV-1451 binding patterns in three autopsy-confirmed non-Alzheimer tauopathy cases.
  
  
  METHODS
  We quantified in vivo retention of [F-18]-AV-1451 and performed autoradiography, [H-3]-AV-1451 binding assays, and quantitative tau measurements in postmortem brain samples from two progressive supranuclear palsy (PSP) cases and a MAPT P301L mutation carrier. They all underwent [F-18]-AV-1451 PET imaging before death.
  
  
  RESULTS
  The three subjects exhibited [F-18]-AV-1451 in vivo retention predominantly in basal ganglia and midbrain. Neuropathological examination confirmed the PSP diagnosis in the first two subjects; the MAPT P301L mutation carrier had an atypical tauopathy characterized by grain-like tau-containing neurites in gray and white matter with heaviest burden in basal ganglia. In all three cases, autoradiography failed to show detectable [F-18]-AV-1451 binding in multiple brain regions examined, with the exception of entorhinal cortex (reflecting incidental age-related neurofibrillary tangles) and neuromelanin-containing neurons in the substantia nigra (off-target binding). The lack of a consistent significant correlation between in vivo [F-18]-AV-1541 retention and postmortem in vitro binding and tau measures in these cases suggests that this ligand has low affinity for tau lesions primarily made of straight tau filaments.
  
  
  CONCLUSIONS
  AV-1451 may have limited utility for in vivo selective and reliable detection of tau aggregates in these non-Alzheimer tauopathies. ANN NEUROL 2017;81:117-128.
authors.affiliation: MassGeneral Institute for NeuroDegenerative Disease, Charlestown, MA.|Department of Neurology, Massachusetts General Hospital, Boston, MA.
authors.forename: Marta
authors.initials: M
authors.lastname: Marquié
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Boston, MA.
authors.forename: Marc D
authors.initials: MD
authors.lastname: Normandin
authors.affiliation: MassGeneral Institute for NeuroDegenerative Disease, Charlestown, MA.|Department of Neurology, Massachusetts General Hospital, Boston, MA.
authors.forename: Avery C
authors.initials: AC
authors.lastname: Meltzer
authors.affiliation: MassGeneral Institute for NeuroDegenerative Disease, Charlestown, MA.|Department of Neurology, Massachusetts General Hospital, Boston, MA.
authors.forename: Michael
authors.initials: M
authors.lastname: Siao Tick Chong
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Boston, MA.
authors.forename: Nicolas V
authors.initials: NV
authors.lastname: Andrea
authors.affiliation: MassGeneral Institute for NeuroDegenerative Disease, Charlestown, MA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Antón-Fernández
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: William E
authors.initials: WE
authors.lastname: Klunk
authors.affiliation: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Chester A
authors.initials: CA
authors.lastname: Mathis
authors.affiliation: Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA.|Geriatric Research Education and Clinical Center, VA Pittsburgh Clinical System, Pittsburgh, PA.
authors.forename: Milos D
authors.initials: MD
authors.lastname: Ikonomovic
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Manik
authors.initials: M
authors.lastname: Debnath
authors.affiliation: MassGeneral Institute for NeuroDegenerative Disease, Charlestown, MA.|Department of Neurology, Massachusetts General Hospital, Boston, MA.|Harvard Neurodiscovery Center, Massachusetts General Hospital, Boston, MA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Bien
authors.affiliation: MassGeneral Institute for NeuroDegenerative Disease, Charlestown, MA.|Department of Neurology, Massachusetts General Hospital, Boston, MA.|Harvard Neurodiscovery Center, Massachusetts General Hospital, Boston, MA.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Vanderburg
authors.affiliation: MassGeneral Institute for NeuroDegenerative Disease, Charlestown, MA.
authors.forename: Isabel
authors.initials: I
authors.lastname: Costantino
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Boston, MA.
authors.forename: Sara
authors.initials: S
authors.lastname: Makaretz
authors.affiliation: MassGeneral Institute for NeuroDegenerative Disease, Charlestown, MA.|Department of Neurology, Massachusetts General Hospital, Boston, MA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: DeVos
authors.affiliation: MassGeneral Institute for NeuroDegenerative Disease, Charlestown, MA.|C.S. Kubik Neuropathology Center, Massachusetts General Hospital, Boston, MA.
authors.forename: Derek H
authors.initials: DH
authors.lastname: Oakley
authors.affiliation: MassGeneral Institute for NeuroDegenerative Disease, Charlestown, MA.|Department of Neurology, Massachusetts General Hospital, Boston, MA.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Gomperts
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Boston, MA.
authors.forename: John H
authors.initials: JH
authors.lastname: Growdon
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Boston, MA.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Domoto-Reilly
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA.
authors.forename: Diane
authors.initials: D
authors.lastname: Lucente
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Boston, MA.
authors.forename: Bradford C
authors.initials: BC
authors.lastname: Dickerson
authors.affiliation: MassGeneral Institute for NeuroDegenerative Disease, Charlestown, MA.|C.S. Kubik Neuropathology Center, Massachusetts General Hospital, Boston, MA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Frosch
authors.affiliation: MassGeneral Institute for NeuroDegenerative Disease, Charlestown, MA.|Department of Neurology, Massachusetts General Hospital, Boston, MA.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Boston, MA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Johnson
authors.affiliation: MassGeneral Institute for NeuroDegenerative Disease, Charlestown, MA.|Department of Neurology, Massachusetts General Hospital, Boston, MA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Gómez-Isla
mesh_terms: D000368:Aged; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D002243:Carbolines / Q000378:metabolism*; D005462:Fluorine Radioisotopes / Q000378:metabolism; D059907:Functional Neuroimaging; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D049268:Positron-Emission Tomography; D011869:Radioligand Assay; D013494:Supranuclear Palsy, Progressive / Q000000981:diagnostic imaging / Q000473:pathology; D024801:Tauopathies / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D014316:Tritium / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D002243:Carbolines; D005462:Fluorine Radioisotopes; C054369:MAPT protein, human; D016875:tau Proteins; D014316:Tritium; C000591008:7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole