Cited by 608Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchRadiopharmaceutical Chemistry and Applications

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

Xia, Chun‐Fang, Arteaga, Janna, Chen, Gang, Gangadharmath, Umesh, Gomez, Luis F., Kasi, Dhanalakshmi, Lam, Chung, Liang, Qianwa, Liu, Changhui, Mocharla, Vani P., Mu, Fanrong, Sinha, Anjana, Su, Helen, Szardenings, A. Katrin, Walsh, Joseph C., Wang, Eric, Yu, Chul, Zhang, Wei, Zhao, Tieming, Kolb, Hartmuth C.·2013·Alzheimer's & Dementia

DOI 10.1016/j.jalz.2012.11.008

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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 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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Self-citation

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: Xia, Chun‐Fang
Liang, Qianwa
Liu, Changhui
Su, Helen
Szardenings, A. Katrin
Zhang, Wei
Kolb, Hartmuth C.
Venue: Alzheimer's & Dementia
Publisher: Wiley
Published: 2013-02-13
Volume: 9
Issue: 6
Pages: 666-676
ISSN: 1552-5260 (ISSN-L)
1552-5279
DOI: 10.1016/j.jalz.2012.11.008
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
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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[ 18 F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease

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