Developments in Tau PET Imaging
Open accessAbstract
The presence of neurofibrillary tangles in the brain is a hallmark feature of several neurodegenerative diseases termed “tauopathies,” including Alzheimer’s disease (AD) and the tau molecular subgroup of frontotemporal lobar degeneration (FTLD-tau). Recently, several positron emission tomography (PET) radiopharmaceuticals targeting abnormal conformations of the tau protein have been developed. To date, six novel tau imaging agents—[18 F]THK523, [18 F]THK5105, [18 F]THK5117, [18 F]T807, [18 F]T808, and [11 C]PBB3—have been described and are considered promising as potential tau radioligands. Tau imaging agents offer the opportunity of in vivo topographical mapping and quantification of tau aggregates in parallel with clinical and cognitive assessments. As such, tau imaging is considered of key importance for progress toward earlier and more accurate diagnosis of tauopathies as well as for the monitoring of therapeutic interventions and drug development. Here, we shed light on the most important developments in tau radiopharmaceuticals, highlighting challenges, possibilities and future directions.
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The larger size of the rat brain facilitates procedures crucial to dementia research, including in vivo brain imaging techniques like MRI and PET, and in vivo electrophysiological recordings and cerebrospinal fluid sampling.
“The larger size of the rat brain facilitates several procedures crucial to dementia research, including in vivo brain imaging techniques like MRI [21] and PET [22–24]”
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MethodBiodistribution and Radiation Dosimetry for the Tau Tracer 18F-THK-5351 in Healthy Human Subjects
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Pan, M., Mukherjee, M. T., Patel, H., Patel, B. A., Constantinescu, C. C., Mirbolooki, M., Liang, C., & Mukherjee, J. (2016) · Synapse · doi:10.1002/syn.21893 · Cited by 14 · see citing works
“With increasing efforts to find treatments and cure for AD, there is much research into imaging plaques and NFT essential to the diagnosis and clinical management of AD (Ariza et al., 2015; Barten and Albright, 2008; Schenk et al. 1999; Verhoeff, 2007; Zimmer et al., 2014).”
BackgroundHong, Y. J., Kim, C. M., Lee, J. H., & Sepulcre, J. (2022) · Scientific Reports · doi:10.1038/s41598-022-18325-2 · Cited by 11 · see citing works
“In brief, the study inclusion criteria for cognitively normal participants were as follows: (1) aged 55–90, (2) normal function in the logical memory II delayed recall test after adjustment for educational level, (3) Mini-Mental State Examination (MMSE)14 score between 24 and 30 (educational level below 8 years can be…”
MethodFrom Neurodegeneration to Brain Health: An Integrated Approach
Petersen, R. B., Lissemore, F. M., Appleby, B. S., Aggarwal, N. T., Boyatzis, R. E., Casadesús, G., Cummings, J., Jack, A. I., Perry, G. L., Safar, J., et al. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150043 · Cited by 13 · see citing works
Yesiltepe, M., Yin, T., Tambini, M., Bao, H., Pan, M., d’Abramo, C., Giliberto, L., Han, X., & D’Adamio, L. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01832-2 · Cited by 10 · see citing works
“The larger size of the rat brain facilitates several procedures crucial to dementia research, including in vivo brain imaging techniques like MRI [21] and PET [22–24], which achieve better spatial resolution in rats, allowing for detailed assessment of neurodegeneration.”
BackgroundAn Aspartyl Cathepsin Targeted PET Agent: Application in an Alzheimer’s Disease Mouse Model
Snir, J. A., Suchý, M., Bindseil, G. A., Kovacs, M. S., Chronik, B. A., Hudson, R. H. E., Pasternak, S., & Bartha, R. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170115 · Cited by 10 · see citing works
“The recent success of A (cid:2) [5] and tau [2, 9, 10] PET imaging in humans should not discourage the testingofnewCAs,whichcouldprovidecomplemen-taryinformationaboutotherpathologicalchanges.”
Szalárdy, L., Zádori, D., Klivènyi, P., & Vécsei, L. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160037 · Cited by 9 · see citing works
“Of note, the ability of 2-(1-{ 6-[(2-(18)F-fluoroethyl)(methyl)amino]-2- naphthyl } ethylidene)malononitrile ( 18 F-FDDNP), a PET tracer previously widely used to visualize both amyloid and Tau pathologies in the brain, has recently been questioned [110].”
Pham, H., Yin, T., & D’Adamio, L. (2022) · PLOS ONE · doi:10.1371/journal.pone.0263546 · Cited by 6 · see citing works
Illuminating Tau Aggregates: Multiscale Approaches for Detection, Imaging, and Understanding
Bhuskute, K. R., Fan, J., & Kaur, A. (2025) · Aggregate · doi:10.1002/agt2.70133 · Cited by 6 · see citing works
Neuroimaging of Mild Traumatic Injury
Capriotti, G., Guarnera, A., Romano, A., Moltoni, G., Granese, G. M., Bozzao, A., & Signore, A. (2025) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2025.06.002 · Cited by 5 · see citing works
Imaging pathological tau in atypical parkinsonian disorders
Coakeley, S., & Strafella, A. P. (2015) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000210 · Cited by 5 · see citing works
“Tau load is correlated with disease severity and cognitive decline [3,12,21].”
BackgroundMolecular Imaging: A New Frontier in Neurotoxicology
Zhang, X., & Paule, M. G. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.65837-3 · Cited by 3 · see citing works
A Cooperative Model for Symmetric Ligand Binding to Protein Fibrils
Smith, M. S., DeGrado, W. F., Grabe, M., & Shoichet, B. K. (2025) · Biochemistry · doi:10.1021/acs.biochem.5c00068 · Cited by 2 · see citing works
Alzheimer's disease: part 2 – the present
Nitríni, R. (2024) · Arquivos de Neuro-Psiquiatria · doi:10.1055/s-0044-1791755 · Cited by 2 · see citing works
“…thedevelopmentof tau-PET, which marksthepresenceof the hyperphosphorylated tau protein present in neuro fi brillary tangles (NFTs) in brain tissue 19,20 and advances in preana-lytical and analytical methods for analyzing biomarkers in CSF, which have greatly increased the reliability of these…”
Gao, H., Cheng, F., Zhang, Z., Yan, B., Liao, P., Zhang, S., Li, D., Chen, F., & Lei, P. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05320-7 · Cited by 1 · see citing works
“In recent times, 18F-T807 has become widely used to target p-Tau [206].”
Khorev, V. S., Mayorova, L. A., Kurkin, S., Badarin, A., & Hramov, A. (2026) · The European Physical Journal Special Topics · doi:10.1140/epjs/s11734-026-02367-y · Cited by 1 · see citing works
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Ventriculomegaly in Aging, Injury and Disease
Acabchuk, R. L. (2016) · OpenCommons at University of Connecticut (University of Connecticut)
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Proxy-PET Building Blocks as a Design Element for Library Synthesis
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Preclinical Longitudinal In Vivo Biomarker Platform for Alzheimer’s Disease Drug Discovery
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Biomarkers for presymptomatic diagnosis and prognosis
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Discovery of a Novel Tau Pet Tracer: Design, Synthesis, Radio-Labeling, and Preclinical EvaluationsPreprint
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Discovery of a Novel Tau Pet Tracer: Design, Synthesis, Radio-Labeling, and Preclinical EvaluationsPreprint
Kuang, W., Yao, D., Zhang, N., Yao, Q., Xie, Y., Tian, R., & Wu, X. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5382846
Discovery of a novel tau PET tracer: Design, synthesis, radio-labeling, and preclinical evaluations
Yao, D., Zhang, N., Yao, Q., Xie, Y., Tian, R., Wu, X., & Kuang, W. (2026) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.118542
The importance of tau tracers in the diagnosis of neurodegenerative diseases
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- Authors
- Zimmer, E. R., Leuzy, A., Gauthier, S., & Rosa-Neto, P.
- Affiliations
- Universidade Federal do Rio Grande do Sul (BR)
- Douglas Mental Health University Institute (CA)
- Venue
- Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques
- Publisher
- Cambridge University Press (CUP)
- Published
- 2014-09
- Volume
- 41
- Issue
- 5
- Pages
- 547-553
- ISSN
- 0317-1671 (ISSN-L)
- 2057-0155
- OpenAlex
- W2080397078
- Cited by
- 60
- References
- 50
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 5 · 2017: 6 · 2016: 13 · 2015: 7
- FWCI
- 1.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Association (MOP-11-51-31, NIRG-12-259245)
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Canadian Institutes of Health Research (#MOP-11-51-31)
- Fonds de Recherche du Québec - Santé
- Topics
- Health Sciences › Medicine › Physiology › 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 › Medical Imaging Techniques and Applications
- Keywords
- tau PET imaging, tauopathy, neurofibrillary tangles, Alzheimer's disease, frontotemporal lobar degeneration, [11C]PBB3, tau aggregation, therapeutic monitoring
- MeSH terms
- Alzheimer Disease, Animals, Brain, Humans, tau Proteins, Radiopharmaceuticals, Tauopathies, Positron-Emission Tomography
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