Cited by 197Alzheimer's disease research and treatmentsRadiopharmaceutical Chemistry and ApplicationsDementia and Cognitive Impairment Research

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A Highly Selective and Specific PET Tracer for Imaging of Tau Pathologies

Zhang, Wei, Arteaga, Janna, Cashion, Daniel K., Chen, Gang, Gangadharmath, Umesh, Gomez, Luis F., Kasi, Dhanalakshmi, Lam, Chung, Liang, Qianwa, Liu, Changhui, Mocharla, Vani P., Mu, Fanrong, Sinha, Anjana, Szardenings, A. Katrin, Wang, Eric, Walsh, Joseph C., Xia, Chunfang, Yu, Chul, Zhao, Tieming, Kolb, Hartmuth C.·2012·Journal of Alzheimer's Disease

DOI 10.3233/jad-2012-120712

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Abstract

Senile plaques and neurofibrillary tangles are prominent neuropathological hallmarks in Alzheimer's disease and are considered to be targets for therapeutic intervention as well as biomarkers for diagnostic in vivo imaging agents. While there are a number of amyloid-β positron emission tomography (PET) tracers currently in different stages of clinical development and commercialization, there have been very few reports on imaging agents selectively targeting tau aggregates. In search of [18F]-PET tracers that possess great binding affinity and selectivity toward tau tangles, we tested more than 900 compounds utilizing a unique screening process. A competitive autoradiography assay was set up to test compounds for binding to native tau tangles and amyloid-β plaques on human brain tissue sections. In our in vitro assays, the 18F labeled compound [18F]-T808 displayed a high level of binding affinity and good selectivity for tau aggregates over amyloid-β plaques. [18F]-T808 showed rapid uptake and washout in rodent brains. Our in vitro and preclinical in vivo studies suggest that [18F]-T808 possesses suitable properties and characteristics to be a specific and selective PET probe for imaging of paired helical filament tau in human brains.

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Authors: Zhang, W., Arteaga, J., Cashion, D. K., Chen, G., Gangadharmath, U., Gomez, L. F., Kasi, D., Lam, C., Liang, Q., Liu, C., Mocharla, V. P., Mu, F., Sinha, A., Szardenings, A. K., Wang, E., Walsh, J. C., Xia, C., Yu, C., Zhao, T., & Kolb, H. C.
Affiliations: Siemens Molecular Imaging, Inc., Culver City, CA, USA
Corresponding author: Kolb, Hartmuth C.
ORCID: Zhang, Wei
Liang, Qianwa
Liu, Changhui
Szardenings, A. Katrin
Kolb, Hartmuth C.
Venue: Journal of Alzheimer's Disease
Publisher: SAGE Publications
Published: 2012-08-22
Volume: 31
Issue: 3
Pages: 601-612
ISSN: 1387-2877 (ISSN-L)
1875-8908
DOI: 10.3233/jad-2012-120712
OpenAlex: W2152648555
Cited by: 195
References: 0
Citations by year: 2026: 3 · 2025: 13 · 2024: 4 · 2023: 12 · 2022: 12 · 2021: 7 · 2020: 6 · 2019: 11 · 2018: 13 · 2017: 18 · 2016: 18 · 2015: 21 · 2014: 25 · 2013: 23 · 2012: 9
FWCI: 17.08
Type: journal article
Language: en
Open access: closed
Locations: Journal of Alzheimer s Disease (publishedVersion)
PubMed (publishedVersion)
Funders: Siemens Medical Solutions USA
National Institute on Aging
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: tau PET tracers
MeSH terms: Animals, Autoradiography, Fluorine Radioisotopes, Humans, Mice, Inbred ICR, Protein Binding, Amyloid beta-Peptides, tau Proteins, Rats, Sprague-Dawley, Radiopharmaceuticals, Positron-Emission Tomography, Mice, Rats, Plaque, Amyloid

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A Highly Selective and Specific PET Tracer for Imaging of Tau Pathologies

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