T807 (AV-1451) (Synonyms: AV-1451)

T807 a novel tau positron emission tomography (PET) tracer.

Aggregated tau protein is a major neuropathological substrate central to the pathophysiology of neurodegenerative diseases such as Alzheimer's disease (AD). In vitro autoradiography results show that [18F]T807 exhibits strong binding to PHF-tau positive human brain sections (Kd=14.6 nM). A comparison of autoradiography and double immunohistochemical staining of PHF-tau and Ab on adjacent sections demonstrates that [18F]T807 binding colocalizes with immunoreactive PHF-tau pathology, but does not highlight Ab plaques[1]. [18F]T807 strongly binds to tau lesions primarily made of paired helical filaments in Alzheimer's brains e.g. intra and extraneuronal tangles and dystrophic neurites. [18F]T807 off-target binding to neuromelanin- and melanin-containing cells and, to a lesser extent, to brain hemorrhagic lesions is identified[2].

[18F]T807 is able to cross the blood-brain barrier and ished out quickly in mice model. [18F]T807 clears rapidly from the brain, with activity values decreasing from 4.43% ID/g at 5 minutes to 0.62% ID/g at 30 minutes. Kidney elimination is a significant clearance pathway, resulting in a maximum tracer concentration of 14.99% ID/g in the kidneys at 5 minutes, which decreases to 5.52% ID/g at 30 minutes. The accumulation of activity in muscle and bone remain relatively low throughout the PET scan[1].

[1]. Xia CF, et al. [(18)F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease. Alzheimers Dement. 2013 Nov;9(6):666-76. [2]. Marquié M, et al. Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue. Ann Neurol. 2015 Nov;78(5):787-800.