Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue

Ann Neurol. 2015 Nov;78(5):787-800. doi: 10.1002/ana.24517. Epub 2015 Sep 25.


Objective: To examine region- and substrate-specific autoradiographic and in vitro binding patterns of positron emission tomography tracer [F-18]-AV-1451 (previously known as T807), tailored to allow in vivo detection of paired helical filament-tau-containing lesions, and to determine whether there is off-target binding to other amyloid/non-amyloid proteins.

Methods: We applied [F-18]-AV-1451 phosphor screen autoradiography, [F-18]-AV-1451 nuclear emulsion autoradiography, and [H-3]-AV-1451 in vitro binding assays to the study of postmortem samples from patients with a definite pathological diagnosis of Alzheimer disease, frontotemporal lobar degeneration-tau, frontotemporal lobar degeneration-transactive response DNA binding protein 43 (TDP-43), progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies, multiple system atrophy, cerebral amyloid angiopathy and elderly controls free of pathology.

Results: Our data suggest that [F-18]-AV-1451 strongly binds to tau lesions primarily made of paired helical filaments in Alzheimer brains (eg, intraneuronal and extraneuronal tangles and dystrophic neurites), but does not seem to bind to a significant extent to neuronal and glial inclusions mainly composed of straight tau filaments in non-Alzheimer tauopathy brains or to lesions containing β-amyloid, α-synuclein, or TDP-43. [F-18]-AV-1451 off-target binding to neuromelanin- and melanin-containing cells and, to a lesser extent, to brain hemorrhagic lesions was identified.

Interpretation: Our data suggest that [F-18]-AV-1451 holds promise as a surrogate marker for the detection of brain tau pathology in the form of tangles and paired helical filament-tau-containing neurites in Alzheimer brains but also point to its relatively lower affinity for lesions primarily made of straight tau filaments in non-Alzheimer tauopathy cases and to the existence of some [F-18]-AV-1451 off-target binding. These findings provide important insights for interpreting in vivo patterns of [F-18]-AV-1451 retention.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging
  • Amyloid / metabolism
  • Autoradiography
  • Brain / diagnostic imaging*
  • Cadaver
  • Carbolines*
  • Dementia / diagnostic imaging
  • Female
  • Frontotemporal Lobar Degeneration / diagnostic imaging
  • Humans
  • Inclusion Bodies / diagnostic imaging
  • Intracranial Hemorrhages / diagnostic imaging
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Radiopharmaceuticals*
  • TDP-43 Proteinopathies / diagnostic imaging
  • Tauopathies / diagnostic imaging*
  • tau Proteins / metabolism*


  • Amyloid
  • Carbolines
  • Radiopharmaceuticals
  • tau Proteins
  • 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole