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

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

Author information

1
MassGeneral Institute for Neurodegenerative Disease, Charlestown, MA.
2
Department of Neurology, Massachusetts General Hospital, Boston, MA.
3
Autonomous University of Barcelona, Medicine Doctoral Studies, Barcelona, Spain.
4
Center for Advanced Medical Imaging Sciences, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
5
Harvard NeuroDiscovery Center, Harvard Medical School, Boston, MA.
6
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA.
7
Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
8
Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
9
Geriatric Research Education and Clinical Center, Veterans Administration Pittsburgh Clinical System, Pittsburgh, PA.
10
C. S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Boston, MA.

Abstract

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.

PMID:
26344059
PMCID:
PMC4900162
DOI:
10.1002/ana.24517
[Indexed for MEDLINE]
Free PMC Article

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