title: PET imaging of neuropathology in tauopathies: progressive supranuclear palsy.
abstract: OBJECTIVE
  Currently [18F]FDDNP is the only PET imaging probe with the ability to visualize hyperphosphorylated tau fibrillar aggregates in living subjects. In this work, we evaluate in vivo [18F]FDDNP labeling of brain neuropathology, primarily tau fibrillar aggregates, in patients with progressive supranuclear palsy (PSP), a human tauopathy usually lacking amyloid-β deposits.
  
  
  METHODS
  Fifteen patients with PSP received [18F]FDDNP PET scanning. [18F]FDDNP distribution volume ratios, in reference to cerebellar gray matter, were determined for cortical and subcortical areas and compared with those of patients with Parkinson's disease with short disease duration, and age-matched control subjects without neurodegenerative disorders.
  
  
  RESULTS
  [18F]FDDNP binding was present in subcortical areas (e.g., striatum, thalamus, subthalamic region, midbrain, and cerebellar white matter) regardless of disease severity, with progressive subcortical and cortical involvement as disease severity increased. Brain patterns of [18F]FDDNP binding were entirely consistent with the known pathology distribution for PSP. High midbrain and subthalamic region [18F]FDDNP binding was distinctive for PSP subjects and separated them from controls and patients with Parkinson's disease.
  
  
  CONCLUSIONS
  These results provide evidence that [18F]FDDNP is a sensitive in vivo PET imaging probe to map and quantify the dynamic regional localization of tau fibrillar aggregates in PSP. Furthermore, [18F]FDDNP PET may provide a tool to detect changes in tau pathology distribution either associated with disease progression or as a treatment biomarker for future tau-specific therapies. Patterns of [18F]FDDNP binding may also be useful in diagnosis early in disease presentation when clinical distinction among neurodegenerative disorders is often difficult.
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095-6948, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kepe
authors.forename: Yvette
authors.initials: Y
authors.lastname: Bordelon
authors.forename: Adam
authors.initials: A
authors.lastname: Boxer
authors.forename: Sung-Cheng
authors.initials: SC
authors.lastname: Huang
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Frederick C
authors.initials: FC
authors.lastname: Thiede
authors.forename: John C
authors.initials: JC
authors.lastname: Mazziotta
authors.forename: Mario F
authors.initials: MF
authors.lastname: Mendez
authors.forename: Natacha
authors.initials: N
authors.lastname: Donoghue
authors.forename: Gary W
authors.initials: GW
authors.lastname: Small
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Barrio
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology*; D002531:Cerebellum / Q000473:pathology; D003342:Corpus Striatum / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008636:Mesencephalon / Q000473:pathology; D008875:Middle Aged; D059906:Neuroimaging; D009570:Nitriles; D010300:Parkinson Disease / Q000473:pathology; D049268:Positron-Emission Tomography; D013494:Supranuclear Palsy, Progressive / Q000473:pathology*; D013788:Thalamus / Q000473:pathology
chemical_list: C444520:2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphthyl)ethylidene)malononitrile; D009570:Nitriles