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[ 18 F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease
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 [(18)F]T807 to tau and Aβ. 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 Aβ on adjacent sections demonstrated that [(18)F]T807 binding colocalized with immunoreactive PHF-tau pathology, but did not highlight Aβ 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.
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“It also has low affinity for amyloid-β and α-synuclein (Xia et al., 2013).”
From Neuroinflammation and protein aggregation co-localize across the frontotemporal dementia spectrum (2020) · cites this paper as Xia et al., 2013
In the citing paper
“18F-AV-1451 was originally developed to bind to paired helical filament tau in Alzheimer’s disease (Zhang et al., 2012; Chien et al., 2013; Xia et al., 2013), and has been extensively used in Alzheimer’s and non-Alzheimer’s diseases.”
From Neuroinflammation and protein aggregation co-localize across the frontotemporal dementia spectrum (2020) · cites this paper as Xia et al., 2013
In the citing paper
“Imaging biomarkers for cortical tau have become available.19,20”
From Positron Emission Tomography Imaging With [ 18 F]flortaucipir and Postmortem Assessment of Alzheimer Disease Neuropathologic Changes (2020) · cites this paper as [20]
In the citing paper
“As expected, in vitro QC-01–175 and T807 displayed a significantly lower affinity for all recombinant immobilized tau forms than the reported KD of T807 for native, aggregated tau filaments from AD brain sections (KD15 nM)”
From Targeted degradation of aberrant tau in frontotemporal dementia patient-derived neuronal cell models (2019) · cites this paper as Xia et al., 2013
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Metadata
- Authors
- Xia, C., Arteaga, J., Chen, G., Gangadharmath, U., Gomez, L. F., Kasi, D., Lam, C., Liang, Q., Liu, C., Mocharla, V. P., Mu, F., Sinha, A., Su, H., Szardenings, A. K., Walsh, J. C., Wang, E., Yu, C., Zhang, W., Zhao, T., & Kolb, H. C.
- Affiliations
- Siemens Healthcare (United States) (US)
- Corresponding author
- Kolb, Hartmuth C.
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2013-02-13
- Volume
- 9
- Issue
- 6
- Pages
- 666-676
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W1974444040
- Cited by
- 605
- References
- 41
- Citations by year
- 2026: 23 · 2025: 36 · 2024: 30 · 2023: 37 · 2022: 43 · 2021: 47 · 2020: 45 · 2019: 53 · 2018: 63 · 2017: 80 · 2016: 68 · 2015: 42 · 2014: 30 · 2013: 8
- FWCI
- 34.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Animals, Autoradiography, Brain, Female, Fluorine Radioisotopes, Humans, Male, Mice, Transgenic, Middle Aged, Protein Binding, Tissue Distribution, Case-Control Studies, Amyloid beta-Peptides, tau Proteins, Positron-Emission Tomography, Mice
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