Cited by 653Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchMedical Imaging Techniques and Applications

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Early Clinical PET Imaging Results with the Novel PHF-Tau Radioligand [F-18]-T807

Chien, David T., Bahri, Shadfar, Szardenings, A. Katrin, Walsh, Joseph C., Mu, Fanrong, Su, Min-Ying, Shankle, William R., Elizarov, Arkadij, Kolb, Hartmuth C.·2013·Journal of Alzheimer's Disease

DOI 10.3233/jad-122059

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Abstract

Aggregates of hyperphosphorylated tau (PHF-tau), such as neurofibrillary tangles, are linked to the degree of cognitive impairment in Alzheimer's disease. We have developed a novel PHF-tau targeting positron emission tomography imaging agent, [F-18]-T807, which may be useful for imaging Alzheimer's disease and other tauopathies. Here in, we describe the first human brain images with [F-18]-T807.

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Background
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Phillips, J. S., Das, S. R., McMillan, C. T., Irwin, D. J., Roll, E. E., Da Re, F., Nasrallah, I. M., Wolk, D. A., & Grossman, M. (2018) · Human Brain Mapping · doi:10.1002/hbm.23874 · Cited by 68
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Background
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Background
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Background
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Background
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Cummings, J. L., Zhou, Y., Stone, A. V., Cammann, D., Tonegawa‐Kuji, R., Cacho, J. R. F., & Cheng, F. (2025) · Nature Communications · doi:10.1038/s41467-025-56690-4 · Cited by 80
“Amyloid positron emission tomography (PET), tau PET, and advanced magnetic resonance imaging (MRI) 88,89 are university-derived, and the revolution in cerebrospinal ﬂ uid (CSF) and blood-based biomarkers re ﬂ ects a critically important contribution of AMCs to the drug development and clinical…”
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Background
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Result
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Self-citation
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Background
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“The first testing in vitro performed on AD brains slices and in vivo testing on MCI, and AD patients indicated that [(18)F]AV-1451 could bind PHF tau and differentiate AD from MCI and HC, thereby initially designating [(18)F]AV-1451 as a promising radiotracer for imaging tau in vivo.(22,25) Further studies also demons…”
Result
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The emerging role of PET imaging in dementia
Iaccarino, L., Sala, A., Caminiti, S. P., & Perani, D. (2017) · F1000Research · doi:10.12688/f1000research.11603.1 · Cited by 52
“To date, three broad groups of radioligands are under extensive evaluation: the 18 F-THK5351, 18 F-THK5117, or 18 F-THK5105 112–114 ; the 18 F-T807 (also known as 18 F-AV1451 or 18 F-Flortaucipir) 115 ; and the 11 C-PBB3 116 .”
Background
Association of amyloid-β CSF/PET discordance and tau load 5 years later
Reimand, J., Collij, L. E., Scheltens, P., Bouwman, F. H., Ossenkoppele, R., & Initiative, A. D. N. (2020) · Neurology · doi:10.1212/wnl.0000000000010739 · Cited by 50
Molecular Imaging Approaches in Dementia
Villemagne, V. L., Barkhof, F., Garibotto, V., Landau, S. M., Nordberg, A. K., & van Berckel, B. N. M. (2021) · Radiology · doi:10.1148/radiol.2020200028 · Cited by 56
“Food and Drug Administration under the name of Tauvid; Avid Radiopharmaceuticals) (42,45) (Fig 2).”
Background
Sex-specific modulation of amyloid-β on tau phosphorylation underlies faster tangle accumulation in females
Wang, Y., Therriault, J., Servaes, S., Tissot, C., Rahmouni, N., Macedo, A. C., Arias, J. F., Mathotaarachchi, S. S., Benedet, A. L., Stevenson, J., et al. (2023) · Brain · doi:10.1093/brain/awad397 · Cited by 54
Neuroimaging the Epileptogenic Process
Shultz, S. R., O'Brien, T. J., Stefanidou, M., et al. (2014) · Neurotherapeutics · doi:10.1007/s13311-014-0258-1 · Cited by 48
Contribution of Alzheimer's biomarkers and risk factors to cognitive impairment and decline across the Alzheimer's disease continuum
Tosun, D., Demir, Z., Veitch, D. P., Weintraub, D. A., Aisen, P. S. S., Jack, C. R., Jagust, W., Petersen, R. C., Saykin, A. J., Shaw, L. M. J., et al. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12480 · Cited by 46
Imaging Frontotemporal Lobar Degeneration
Diehl‐Schmid, J., Onur, O. A., Kuhn, J., GRUPPE, T. L., & Drzezga, A. E. (2014) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-014-0489-x · Cited by 49
Modeling Prion-Like Processing of Tau Protein in Alzheimer’s Disease for Pharmaceutical Development
Wischik, C. M., Schelter, B. O., Wischik, D., Storey, J. M. D., & Harrington, C. R. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170727 · Cited by 49
Role of Neuroimaging as a Biomarker for Neurodegenerative Diseases
Shimizu, S., Hirose, D., Hatanaka, H., Takenoshita, N., Kaneko, Y., Ogawa, Y., Sakurai, H., & Hanyu, H. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00265 · Cited by 52
“The radiotracers used to image tau neurofibrillary tangle deposition in living AD patient brains are 18F-FDDNP (43), 18F-AV1451 (44), 11C-PBB3 (45), and 18F-THK5351 (46).”
Background
Positron emission tomography of tau in Iraq and Afghanistan Veterans with blast neurotrauma
Robinson, M. E., McKee, A. C., Salat, D. H., Rasmusson, A. M., Radigan, L. J., Catana, C., Milberg, W., & McGlinchey, R. E. (2019) · NeuroImage Clinical · doi:10.1016/j.nicl.2019.101651 · Cited by 47
“We utilized [(18)F]-T807/AV1451 (Flortaucipir) (Chien et al., 2013; Xia et al., 2013), a tau-binding PET tracer in a sample of primarily military Veterans (n=17) drawn from those enrolled in TRACTS (McGlinchey et al.”
Dementia spectrum disorders: lessons learnt from decades with PET research
Wilson, H., Pagano, G., & Politis, M. (2019) · Journal of Neural Transmission · doi:10.1007/s00702-019-01975-4 · Cited by 50
Multi-modal latent factor exploration of atrophy, cognitive and tau heterogeneity in Alzheimer’s disease
Sun, N., Mormino, E. C., Chen, J., Sabuncu, M. R., & Yeo, B. T. T. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.116043 · Cited by 47
“The advent of 18 F-Flortaucipir, a PET tracer with high af ﬁ nity for paired helical ﬁ lament Tau, provides an exciting opportunity to investigate regional NFTs in vivo (Chien et al., 2013).”
Influential
Sex differences in off-target binding using tau positron emission tomography
Smith, R. A., Strandberg, O. T., Leuzy, A., Betthauser, T. J., Johnson, S. C., Pereira, J. B., & Hansson, O. (2021) · NeuroImage Clinical · doi:10.1016/j.nicl.2021.102708 · Cited by 46
Advanced Overview of Biomarkers and Techniques for Early Diagnosis of Alzheimer’s Disease
Rani, S., Dhar, S. B., Khajuria, A., Gupta, D., Jaiswal, P. K., Singla, N., Kaur, M., Singh, G., & Barnwal, R. P. (2023) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-023-01330-y · Cited by 48
“These NFTs are responsible for neuron degradation, mitochondria defects, brain atrophy, and cell death (Maji et al. 2010; Chien et al. 2013; Babić et al. 2014).”
Background
Imaging the Role of Amyloid in PD Dementia and Dementia with Lewy Bodies
Gomperts, S. N. (2014) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-014-0472-6 · Cited by 47
Quantification of Tau Load Using [18F]AV1451 PET
Golla, S. S. V., Timmers, T., Ossenkoppele, R., Groot, C., Verfaillie, S. C. J., Scheltens, P., van der Flier, W. M., Schwarte, L. A., Mintun, M. A., Devous, M. D., et al. (2017) · Molecular Imaging and Biology · doi:10.1007/s11307-017-1080-z · Cited by 45
“In most of the previous studies, [(18)F]AV1451 uptake has typically been measured using semi-quantitative methods, such as the standard uptake value ratio (SUVr) [5, 8, 9].”
Longitudinal tau and metabolic PET imaging in relation to novel CSF tau measures in Alzheimer’s disease
Leuzy, A., Cicognola, C., Chiotis, K., Saint‐Aubert, L., Lemoine, L., Andreasen, N., Zetterberg, H., Ye, K., Blennow, K., Höglund, K., et al. (2019) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-018-4242-6 · Cited by 48
“One such ligand is [(18)F]flortaucipir (formerly known as [(18)F]T-807 and [(18)F]AV1451) [2, 3], and studies examining the relationship between [(18)F]flortaucipir uptake and CSF tau levels have shown modest positive correlations in cognitively unim-”
Background
The therapeutic potential of PROTACs
Benowitz, A. B., Jones, K. L., & Harling, J. D. (2020) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2021.1840553 · Cited by 47
Clinical validity of increased cortical uptake of [18F]flortaucipir on PET as a biomarker for Alzheimer’s disease in the context of a structured 5-phase biomarker development framework
Wolters, E. E., Dodich, A., Boccardi, M., Corre, J., Drzezga, A. E., Hansson, O., Nordberg, A. K., Frisoni, G. B., Garibotto, V., & Ossenkoppele, R. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-020-05118-w · Cited by 48
Neuroimaging assessment of early and late neurobiological sequelae of traumatic brain injury: implications for CTE
Sundman, M., Doraiswamy, P. M., & Morey, R. A. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00334 · Cited by 46
“Significantly, unlike other 18F PET probes,18F-T807 exhibited very low non-specific binding in both the gray matter and white matter of the brain yielding improved contrast and, thus, greater clinical utility (Chien et al., 2013).”
Background
Structure–Activity Relationship Study of Heterocyclic Phenylethenyl and Pyridinylethenyl Derivatives as Tau-Imaging Agents That Selectively Detect Neurofibrillary Tangles in Alzheimer’s Disease Brains
Matsumura, K., Ono, M., Kitada, A., Watanabe, H., Yoshimura, M., Iikuni, S., Kimura, H., Okamoto, Y., Ihara, M., & Saji, H. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00440 · Cited by 43
Identification of a major radiometabolite of [ 11 C]PBB3
Hashimoto, H., Kawamura, K., Takei, M., Igarashi, N., Fujishiro, T., Shiomi, S., Watanabe, R., Muto, M., Furutsuka, K., Ito, T., et al. (2015) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2015.08.006 · Cited by 44
Cysteine-Independent Inhibition of Alzheimer's Disease-like Paired Helical Filament Assembly by Leuco-Methylthioninium (LMT)
Al‐Hilaly, Y. K., Pollack, S. J., Rickard, J. E., Simpson, M. C., Raulin, A., Baddeley, T. C., Schellenberger, P., Storey, J. M. D., Harrington, C. R., Wischik, C. M., et al. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.08.010 · Cited by 42
Regional [18F]flortaucipir PET is more closely associated with disease severity than CSF p-tau in Alzheimer’s disease
Wolters, E. E., Ossenkoppele, R., Verfaillie, S. C. J., Coomans, E. M., Timmers, T., Visser, D., Tuncel, H., Golla, S. S. V., Windhorst, A. D., Boellaard, R., et al. (2020) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-020-04758-2 · Cited by 45
Alternative approaches for PET radiotracer development in Alzheimer's disease: imaging beyond plaque
Holland, J. P., Liang, S. H., Rotstein, B. H., Collier, T. L., Stephenson, N. A., Greguric, I. D., & Vasdev, N. (2013) · Journal of Labelled Compounds and Radiopharmaceuticals · doi:10.1002/jlcr.3158 · Cited by 43
Data‐driven approaches for tau‐PET imaging biomarkers in Alzheimer's disease
Vogel, J. W., Mattsson, N., Iturria‐Medina, Y., Strandberg, O. T., Schöll, M., Dansereau, C. L., Villeneuve, S., van der Flier, W. M., Scheltens, P., Bellec, P., et al. (2018) · Human Brain Mapping · doi:10.1002/hbm.24401 · Cited by 44
“[(18)F] AV1451 binds paired helical filaments of tau with high affinity and selectivity (Chien et al., 2013; Lowe et al., 2016; Marquié et al., 2015, 2017; Xia et al., 2013), and can be used to investigate the distribution of tau pathology in the living human brain.”
Background
Mesial temporal tau is related to worse cognitive performance and greater neocortical tau load in amyloid-β–negative cognitively normal individuals
Groot, C., Doré, V., Robertson, J. S., Burnham, S. C., Savage, G. R., Ossenkoppele, R., Rowe, C. C., & Villemagne, V. L. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.09.017 · Cited by 41
Imaging of Tau Pathology in Neurodegenerative Diseases: An Update
Beyer, L., & Brendel, M. (2020) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2020.12.004 · Cited by 44
“Since the first human brain imaging publication of [ 18 F]flortaucipir in 2013 14 , binding affinities have been investigated intensively in vitro and in vivo .”
Discovery of N-(Pyridin-4-yl)-1,5-naphthyridin-2-amines as Potential Tau Pathology PET Tracers for Alzheimer’s Disease
Rombouts, F. J. R., Andrés, J.-I., Ariza, M., Alonso, J. M., Austin, N. E., Bottelbergs, A., Chen, L., Chupakhin, V., Cleiren, E., Fierens, K., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01173 · Cited by 42
[11C]PBB3—a new PET ligand that identifies tau pathology in the brains of patients with AD
Wood, H. B. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.216 · Cited by 42
Dementia with Lewy bodies can be well‐differentiated from Alzheimer's disease by measurement of brain acetylcholinesterase activity—a [11C]MP4A PET study
Shimada, H., Hirano, S., Sinotoh, H., Ota, T., Tanaka, N., Sato, K., Yamada, M., Fukushi, K., Irie, T., Zhang, M. R., et al. (2015) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.4338 · Cited by 40
“…tracking of amyloid (Klunk et al., 2004; Rowe et al., 2008; Choi et al., 2009; Juréus et al., 2010; Vandenberghe et al., 2010) and tau pathologies (Chien et al., 2013; Maruyama et al., 2013; Okamura et al., 2013) using positron emission tomography (PET) is expected to be a surrogate marker that…”
Background
First Human Use of a Radiopharmaceutical Prepared by Continuous-Flow Microfluidic Radiofluorination: Proof of Concept with the Tau Imaging Agent [ 18 F]T807
Liang, S. H., Yokell, D. L., Normandin, M. D., Rice, P. A., Jackson, R. N., Shoup, T. M., Brady, T. J., Fakhri, G. E., Collier, T. L., & Vasdev, N. (2014) · Molecular Imaging · doi:10.2310/7290.2014.00025 · Cited by 40
“Fluorine 18-labeled 7-(6fluoropyridin-3-yl)-5H-pyrido[4,3-b]indole ([(18)F]T807) is a PET radiotracer for imaging paired helical filaments of tau.(13,14) We recently reported a simplified one-step From the Center for Advanced Medical Imaging Sciences, Division of Nuclear Medicine and Molecular Imaging, Massachusetts G…”
Background
Abnormalities of plasma cytokines and spleen in senile APP/PS1/Tau transgenic mouse model
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“Concentrations of Aβ (1-42) in the CSF (A) and plasma (B) of 3xTg-AD”
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“In addition, two related radioligands, [(18)F]T807 and [(18)F]T808, have high affinity and selectivity for p-tau in humans.(121,122) Multiple clinical trials are under way to investigate the use of [(18)F]T807 as a potential biomarker of CTE.”
Regional Tau Correlates of Instrumental Activities of Daily Living and Apathy in Mild Cognitive Impairment and Alzheimer’s Disease Dementia
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MicroPET imaging and transgenic models: a blueprint for Alzheimer's disease clinical research
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Authors: Chien, D. T., Bahri, S., Szardenings, A. K., Walsh, J. C., Mu, F., Su, M.-Y., Shankle, W. R., Elizarov, A., & Kolb, H. C.
Affiliations: Siemens Molecular Imaging, Inc., Culver City, CA, USA
University of California, Irvine (US)
Hoag Memorial Hospital Presbyterian (US)
ORCID: Bahri, Shadfar
Szardenings, A. Katrin
Su, Min-Ying
Shankle, William R.
Kolb, Hartmuth C.
Venue: Journal of Alzheimer's Disease
Publisher: SAGE Publications
Published: 2013-06-20
Volume: 34
Issue: 2
Pages: 457-468
ISSN: 1387-2877 (ISSN-L)
1875-8908
DOI: 10.3233/jad-122059
OpenAlex: W4235092975
Cited by: 651
References: 0
Citations by year: 2026: 14 · 2025: 26 · 2024: 19 · 2023: 31 · 2022: 40 · 2021: 51 · 2020: 49 · 2019: 49 · 2018: 57 · 2017: 88 · 2016: 87 · 2015: 62 · 2014: 54 · 2013: 23
FWCI: 52.32
Type: journal article
Language: en
Open access: closed
Locations: Journal of Alzheimer s Disease (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 › Medical Imaging Techniques and Applications
Keywords: PHF-tau
MeSH terms: Aged, Aged, 80 and over, Alzheimer Disease, Carbolines, Female, Fluorine Radioisotopes, Frontal Lobe, Humans, Male, Middle Aged, Phosphorylation, tau Proteins, Early Diagnosis, Positron-Emission Tomography

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Early Clinical PET Imaging Results with the Novel PHF-Tau Radioligand [F-18]-T807

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