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 [18F]T807 to tau and Aβ. Brain uptake and biodistribution of [18F]T807 in mice were also tested. Results: In vitro autoradiography results show that [18F]T807 exhibits strong binding to PHF-tau-positive human brain sections. A dissociation constant (Kd) of [18F]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 [18F]T807 binding colocalized with immunoreactive PHF-tau pathology, but did not highlight Aβ plaques. In vivo studies in mice demonstrated that [18F]T807 was able to cross the blood-brain barrier and washed out quickly. Conclusions: [18F]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.
Original language | English |
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Pages (from-to) | 666-676 |
Number of pages | 11 |
Journal | Alzheimer's and Dementia |
Volume | 9 |
Issue number | 6 |
DOIs | |
State | Published - Nov 2013 |
ASJC Scopus Subject Areas
- Epidemiology
- Health Policy
- Developmental Neuroscience
- Clinical Neurology
- Geriatrics and Gerontology
- Cellular and Molecular Neuroscience
- Psychiatry and Mental health
Keywords
- Alzheimer's disease
- Amyloid β
- Autoradiography
- Imaging
- Tau
- [F]T807