Cited by 133Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsMedical Imaging Techniques and Applications

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Effect of Off-Target Binding on 18F-Flortaucipir Variability in Healthy Controls Across the Life Span

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Baker, Suzanne L., Harrison, Theresa M., Maass, Anne, La Joie, Renaud, Jagust, William J.·2019·Journal of Nuclear Medicine

DOI 10.2967/jnumed.118.224113PMC PMC6785795

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Abstract

Measuring early tau accumulation is important in studying aging and Alzheimer disease and is only as accurate as the signal-to-noise ratio of the tracer. Along with aggregated tau in the form of neurofibrillary tangles, 18F-flortaucipir has been reported to bind to neuromelanin, monoamine oxidase, calcifications, iron, leptomeningeal melanocytes, and microhemorrages. Although 18F-flortaucipir successfully differentiates healthy controls (HCs) from subjects with Alzheimer disease, variability exists in the cortical signal in amyloid-negative HCs. We aimed to explore the relationship between off-target binding signal and variability in the cortical signal in HCs. Methods: Subjects (n = 139) received 11C-Pittsburgh compound B (PIB) and 18F-flortaucipir PET scans and a magnetization-prepared rapid gradient echo MRI scan. PET frames were realigned and coregistered to the MR images, which were segmented using FreeSurfer. In amyloid-negative HCs (n = 90; age range, 21–94 y), 7 nonspecific or off-target binding regions were considered: caudate, pallidum, putamen, thalamus, cerebellar white matter, hemispheric white matter, and choroid plexus. These regions of interest were assigned to 3 similarly behaving groups using principle components analysis, exploratory factor analysis, and Pearson correlations for caudate, putamen, and pallidum (also correlated with age); thalamus and white matter; and choroid plexus. In amyloid-negative HCs with 11C-PIB and 18F-flortaucipir scans, correlations were calculated between white and gray matter before and after partial-volume correction. Results: The correlation between white and gray matter disappeared after partial-volume correction in 11C-PIB (r2 = 0) but persisted for 18F-flortaucipir (r2 = 0.27), demonstrating that the correlation between white and gray matter signal in 18F-flortaucipir is not solely due to partial-volume effects. A linear regression showed that off-target signal from putamen and thalamus together explained 64% of the variability in the cortical signal in amyloid-negative HCs (not seen in amyloid-positive HCs). Variability in amyloid-negative HCs but not amyloid-positive HCs correlated with white matter signal (unrelated to partial-volume effects) and age-related off-target signal (possibly related to iron load). Conclusion: The noise in the 18F-flortaucipir measurement could pose challenges when studying early tau accumulation.

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“18F-flortaucipir (also known as T807 and 18F-AV-1451) is a PET tracer that binds with high affinity to paired helical filament tau in neurofibrillary tangles (2,3).”
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Authors: Baker, S. L., Harrison, T. M., Maass, A., La Joie, R., & Jagust, W. J.
Affiliations: Lawrence Berkeley National Laboratory (US)
University of California, Berkeley (US)
German Center for Neurodegenerative Diseases (DE)
ORCID: Baker, Suzanne L.
Harrison, Theresa M.
Maass, Anne
Jagust, William J.
Venue: Journal of Nuclear Medicine
Publisher: Society of Nuclear Medicine
Published: 2019-03-15
Volume: 60
Issue: 10
Pages: 1444-1451
ISSN: 0161-5505 (ISSN-L)
2159-662X
DOI: 10.2967/jnumed.118.224113
PMC: PMC6785795
OpenAlex: W2921651552
Cited by: 132
References: 38
Citations by year: 2026: 19 · 2025: 13 · 2024: 18 · 2023: 16 · 2022: 20 · 2021: 19 · 2020: 22 · 2019: 5
FWCI: 13.15
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Nuclear Medicine (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
eScholarship (California Digital Library) (submittedVersion)
DZNE Pub (submittedVersion)
Funders: Biogen
BioClinica
National Institutes of Health (AG034570)
Genentech
National Institute on Aging (F32AG057107, R01AG034570)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
Keywords: 18F-flortaucipir, off-target binding, tau PET, partial volume correction, 11C-Pittsburgh compound B, thalamus, putamen, choroid plexus, aging, Alzheimer's disease, signal-to-noise ratio, neurofibrillary tangles
MeSH terms: Adult, Aged, Aged, 80 and over, Aniline Compounds, Brain, Brain Mapping, Carbolines, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Protein Binding, Thiazoles, Reproducibility of Results, Linear Models, Positron-Emission Tomography, Young Adult, Healthy Volunteers

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Effect of Off-Target Binding on 18F-Flortaucipir Variability in Healthy Controls Across the Life Span

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