HAI Book 2025 - Flipbook - Page 457
Saturnino Guarino, Dinahlee
In vitro binding of the tau PET tracer [3H]JSS20-183A and its comparison
with PI-2620, T807 and PM-PBB3 in human postmortem brain tissue
Dinahlee Saturnino Guarino1, Jeffrey Stehouwer2, John L. Robinson3, Theresa Schuck3,
Edward B. Lee3,4, Virginia M. Lee3,4, Neil Vasdev5,6, Chester A. Mathis2, Robert H. Mach1
1
Department of Radiology, University of Pennsylvania, Philadelphia, PA, US
Department of Radiology, University of Pittsburgh, Pittsburgh, PA, US
3
Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Institute on
Aging, University of Pennsylvania, Philadelphia, PA, US
4
Penn Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia,
PA, US
5
Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health,
Toronto, ON, CA
6
Department of Psychiatry, University of Toronto, Toronto, ON, CA
7
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA,
US
2
Objectives: Imaging of tau inclusions will help in the diagnosis, prevention and treatment of neurodegenerative
disorders. The goals of this study were to evaluate the utility of [3H]JSS20-183A and to compare its binding
properties with three tau positron emission tomography (PET) tracers, PI-2620, T807 (AV-1451, flortaucipir,
Tauvid) and PM-PBB3, in the same human postmortem tissue to understand the binding profile of each
radiotracer.
Methods: [3H]JSS20-183A in vitro autoradiography and immunohistochemistry studies were conducted in
postmortem samples from patients with Alzheimer's disease, AD with Lewy bodies, frontotemporal lobar
degeneration-tau (Pick9s disease, progressive supranuclear palsy and corticobasal degeneration), frontotemporal
lobar degeneration-Tar DNA-binding protein 43 (TDP-43), Parkinson9s disease, Parkinson9s disease with dementia,
Dementia with Lewy Bodies, Multiple system atrophy and elderly controls free of pathology. Brain sections were
stained for tau, A´ and ³-synuclein and compared to JSS20-183A autoradiography on adjacent sections. Binding
and competition assays to compare the regional distribution of the four tau tracers were also conducted using
autoradiography.
Results: The binding profile of JSS20-183A with respect to tau isoforms in various neurodegenerative diseases
was: 3R/4R tau (AD) > 3R tau (Pick's disease) > 4R tau (CBD) > 4R tau (PSP). There is no evidence of binding to
lesions containing ³-synuclein or TDP-43. [3H]JSS20-183A, [3H]PI-2620, [3H]T807, [3H]PM-PBB3 autoradiography
in AD brains showed similar binding for the four tracers. Results from CBD, PSP and Pick9s cases showed high
binding of [3H]JSS20-183A and [3H]PM-PBB3 and lower specific binding of [3H]PI-2620 and [3H]T807.
Discussion: Our results suggest that JSS20-183A holds promise as a radiotracer for the detection of tau
pathology in AD and the non-AD tauopathies. We also demonstrated the different binding properties among the
second-generation tau PET tracers, which may assist in further understanding of tau heterogeneity in
neurodegenerative disorders.
Keywords: Alzheimer’s disease, non-AD-tauopathies, autoradiography,Tau imaging, Tau PET tracers
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