[(18)F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease.

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Xia CF, Arteaga J, Chen G, Gangadharmath U, Gomez LF, Kasi D, Lam C, Liang Q, Liu C, Mocharla VP, Mu F, Sinha A, Su H, Szardenings AK, Walsh JC, Wang E, Yu C, Zhang W, Zhao T, Kolb HC

[(18)F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease.

Alzheimers Dement. 2013 Nov;9(6):666-76. doi: 10.1016/j.jalz.2012.11.008. Epub 2013 Feb 12.

PubMed ID

23411393 [ View in PubMed

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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 Abeta rather than synthetic tau aggregates or Abeta fibrils generated in vitro to measure the affinity and selectivity of [(18)F]T807 to tau and Abeta. Brain uptake and biodistribution of [(18)F]T807 in mice were also tested. RESULTS: In vitro autoradiography results show that [(18)F]T807 exhibits strong binding to PHF-tau-positive human brain sections. A dissociation constant (Kd) of [(18)F]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 Abeta on adjacent sections demonstrated that [(18)F]T807 binding colocalized with immunoreactive PHF-tau pathology, but did not highlight Abeta plaques. In vivo studies in mice demonstrated that [(18)F]T807 was able to cross the blood-brain barrier and washed out quickly. CONCLUSIONS: [(18)F]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.

DrugBank Data that Cites this Article

Drugs

Flortaucipir F-18

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Flortaucipir F-18	Microtubule-associated protein tau	Protein	Humans	Yes	Binder	Details