[18F]‐THK5351 PET correlates with topology and symptom severity in progressive supranuclear palsy
Open accessAbstract
Progressive supranuclear palsy (PSP) is a neurodegenerative movement disorder characterized by deposition of fibrillar aggregates of 4R tau-protein in neurons and glial cells of the brain. These deposits are a key neuropathological finding, allowing a diagnosis of “definite PSP”, which is usually established post mortem. To date criteria for clinical diagnosis of PSP in vivo do not include biomarkers of tau pathology. For intervention trials, it is increasingly important to i) establish biomarkers for an early diagnosis and ii) to develop biomarkers that correlate with disease progression of PSP. [18F]-THK5351 is a novel PET-ligand that may afford in vivo visualization and quantification of tau-related alterations. We investigated binding characteristics of [18F]-THK5351 in patients with clinically diagnosed PSP and correlate tracer uptake with clinical findings. Eleven patients (68.4±7.4 y; N=6 female) with probable PSP according to current clinical criteria and nine healthy controls (71.7±7.2 y; N=4 female) underwent [18F]-THK5351 PET scanning. Voxel-wise statistical parametric comparison and volume-of-interest based quantification of standardized-uptake-values (SUV) were conducted using the cerebellar cortex as reference region. We correlated disease severity as measured with the help of the PSP Rating Scale (PSPRS) as well as several other clinical parameters with the individual PET findings. By voxel-wise mapping of [18F]-THK5351 uptake in the patient group we delineated typical distribution patterns that fit to known tau topology for PSP post mortem. Quantitative analysis indicated the strongest discrimination between PSP patients and healthy controls based on tracer uptake in the midbrain (+35%; p=3.01E-7; Cohen’s d: 4.0), followed by the globus pallidus, frontal cortex, and medulla oblongata. Midbrain [18F]-THK5351 uptake correlated well with clinical severity as measured by PSPRS (R=0.66; p=0.026). OCT and MRI delineated PSP patients from healthy controls by use of established discrimination thresholds but only OCT did as well correlate with clinical severity (R=0.79; p=0.024). Regional [18F]-THK5351 binding patterns correlated well with the established post mortem distribution of lesions in PSP and with clinical severity. The contribution of possible MAO-B binding to the [18F]-THK5351 signal needs to be further evaluated, but nevertheless [18F]-THK5351 PET may still serve as valuable biomarker for diagnosis of PSP.
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Earlier PET investigations have detected alterations in PSP with ligands for tau and for microglial activation.
“Previous positron emission tomography (PET) has indicated changes in PSP using ligands targeting tau8–16 and microglial activation17,18.”
From Neuroinflammation and Tau Colocalize in vivo in Progressive Supranuclear Palsy (2020) · cites this paper as [15]
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Neuroinflammation and Tau Colocalize in vivo in Progressive Supranuclear Palsy
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- Authors
- Brendel, M., Schönecker, S., Höglinger, G., Lindner, S., Havla, J., Blautzik, J., Sauerbeck, J., Rohrer, G., Zach, C., Vettermann, F., Lang, A. E., Golbe, L., Nübling, G., Bartenstein, P., Furukawa, K., Ishiki, A., Bötzel, K., Danek, A., Okamura, N., Levin, J., & Rominger, A.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- German Center for Neurodegenerative Diseases (DE)
- Institut für Klinische Neuroimmunologie (DE)
- University of Toronto (CA)
- Rutgers, The State University of New Jersey (US)
- Tohoku Medical and Pharmaceutical University (JP)
- Tohoku University (JP)
- Corresponding author
- Levin, Johannes
- Rominger, Axel
- ORCID
- Brendel, Matthias
- Schönecker, Sonja
- Höglinger, Günter
- Lindner, Simon
- Havla, Joachim
- Blautzik, Janusch
- Sauerbeck, Julia
- Zach, Christian
- Vettermann, Franziska
- Lang, Anthony E.
- Golbe, Lawrence
- Nübling, Georg
- Bartenstein, Peter
- Furukawa, Katsutoshi
- Bötzel, Kai
- Danek, Adrian
- Okamura, Nobuyuki
- Levin, Johannes
- Rominger, Axel
- Venue
- Frontiers in Aging Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2018-01-17
- Volume
- 9
- Pages
- 440-440
- ISSN
- 1663-4365 (ISSN-L)
- PMC
- PMC5776329
- OpenAlex
- W2794224336
- Cited by
- 72
- References
- 45
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 6 · 2023: 7 · 2022: 9 · 2021: 11 · 2020: 13 · 2019: 9 · 2018: 8
- FWCI
- 6.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Aging Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion, cc-by)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- DZNE Pub (submittedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft (HO2402/6‐2)
- NOMIS Stiftung
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- progressive supranuclear palsy, 18F-THK5351, tau PET imaging, clinical severity, PSP Rating Scale, globus pallidus, disease progression biomarkers, optical coherence tomography, magnetic resonance imaging, postmortem neuropathology, early diagnosis, standardized uptake value, neurodegenerative movement disorders
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