A highly selective and specific PET tracer for imaging of tau pathologies
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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18F-AV-1451 was originally developed to bind paired helical filament tau in Alzheimer's disease.
“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 Zhang et al., 2012
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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.
- 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
- 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
- Health Sciences › Medicine › Physiology › 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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