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    Original Investigation
    July 7, 2020

    Assessment of 18F-PI-2620 as a Biomarker in Progressive Supranuclear Palsy

    Author Affiliations
    • 1Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany
    • 2Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany
    • 3Department of Nuclear Medicine, University Hospital Cologne, Cologne, Germany
    • 4Department of Neurology, University Hospital Cologne, Cologne, Germany
    • 5German Center for Neurodegenerative Diseases (DZNE), Bonn-Cologne, Germany
    • 6InviCRO LLC, Boston, Massachusetts
    • 7Molecular Neuroimaging, A Division of InviCRO, New Haven, Connecticut
    • 8Department of Neurology, University Hospital of Munich, LMU Munich, Munich, Germany
    • 9Department of Neurology, Hannover Medical School, Hannover, Germany
    • 10Department of Psychiatry, University Hospital Cologne, Cologne, Germany
    • 11Center for Memory Disorders, University Hospital Cologne, Cologne, Germany
    • 12Department of Neurology, University of Leipzig, Leipzig, Germany
    • 13Clinic for Cognitive Neurology, University of Leipzig, Leipzig, Germany
    • 14LIFE–Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
    • 15Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
    • 16Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Jülich, Germany
    • 17Life Molecular Imaging GmbH, Berlin, Germany
    • 18Center for Neuropathology and Prion Research, University Hospital of Munich, LMU Munich, Munich, Germany
    • 19German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
    • 20Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
    • 21Department of Molecular Imaging & Therapy, Austin Health, Heidelberg, Victoria, Australia
    • 22Department of Medicine, Austin Health, The University of Melbourne, Melbourne, Victoria, Australia
    • 23Department of Neurology, Technical University Munich, Munich, Germany
    JAMA Neurol. Published online July 7, 2020. doi:10.1001/jamaneurol.2020.2526
    Key Points

    Question  Can tau–positron emission tomography imaging with the novel tau radiotracer 18F-PI-2620 differentiate patients with progressive supranuclear palsy (PSP) from healthy controls and controls with disease?

    Findings  In this cross-sectional study of 60 patients with PSP, 10 healthy controls, and 20 controls with disease, there was significantly higher 18F-PI-2620 binding in target regions of patients with PSP compared with controls regardless of disease severity. Individual patients with PSP with Richardson syndrome were separated with high sensitivity and specificity.

    Meaning  18F-PI-2620 tau–positron emission tomography differentiates patients with PSP from controls at the single-patient level, potentially facilitating a more reliable diagnosis.


    Importance  Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy. Region-specific tau aggregates establish the neuropathologic diagnosis of definite PSP post mortem. Future interventional trials against tau in PSP would strongly benefit from biomarkers that support diagnosis.

    Objective  To investigate the potential of the novel tau radiotracer 18F-PI-2620 as a biomarker in patients with clinically diagnosed PSP.

    Design, Setting, and Participants  In this cross-sectional study, participants underwent dynamic 18F-PI-2620 positron emission tomography (PET) from 0 to 60 minutes after injection at 5 different centers (3 in Germany, 1 in the US, and 1 in Australia). Patients with PSP (including those with Richardson syndrome [RS]) according to Movement Disorder Society PSP criteria were examined together with healthy controls and controls with disease. Four additionally referred individuals with PSP-RS and 2 with PSP–non-RS were excluded from final data analysis owing to incomplete dynamic PET scans. Data were collected from December 2016 to October 2019 and were analyzed from December 2018 to December 2019.

    Main Outcomes and Measures  Postmortem autoradiography was performed in independent PSP-RS and healthy control samples. By in vivo PET imaging, 18F-PI-2620 distribution volume ratios were obtained in globus pallidus internus and externus, putamen, subthalamic nucleus, substantia nigra, dorsal midbrain, dentate nucleus, dorsolateral, and medial prefrontal cortex. PET data were compared between patients with PSP and control groups and were corrected for center, age, and sex.

    Results  Of 60 patients with PSP, 40 (66.7%) had RS (22 men [55.0%]; mean [SD] age, 71 [6] years; mean [SD] PSP rating scale score, 38 [15]; score range, 13-71) and 20 (33.3%) had PSP–non-RS (11 men [55.0%]; mean [SD] age, 71 [9] years; mean [SD] PSP rating scale score, 24 [11]; score range, 11-41). Ten healthy controls (2 men; mean [SD] age, 67 [7] years) and 20 controls with disease (of 10 [50.0%] with Parkinson disease and multiple system atrophy, 7 were men; mean [SD] age, 61 [8] years; of 10 [50.0%] with Alzheimer disease, 5 were men; mean [SD] age, 69 [10] years). Postmortem autoradiography showed blockable 18F-PI-2620 binding in patients with PSP and no binding in healthy controls. The in vivo findings from the first large-scale observational study in PSP with 18F-PI-2620 indicated significant elevation of tracer binding in PSP target regions with strongest differences in PSP vs control groups in the globus pallidus internus (mean [SD] distribution volume ratios: PSP-RS, 1.21 [0.10]; PSP–non-RS, 1.12 [0.11]; healthy controls, 1.00 [0.08]; Parkinson disease/multiple system atrophy, 1.03 [0.05]; Alzheimer disease, 1.08 [0.06]). Sensitivity and specificity for detection of PSP-RS vs any control group were 85% and 77%, respectively, when using classification by at least 1 positive target region.

    Conclusions and Relevance  This multicenter evaluation indicates a value of 18F-PI-2620 to differentiate suspected patients with PSP, potentially facilitating more reliable diagnosis of PSP.