Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/25306
Title: Assessment of 18F-PI-2620 as a Biomarker in Progressive Supranuclear Palsy.
Austin Authors: Brendel, Matthias;Barthel, Henryk;van Eimeren, Thilo;Marek, Ken;Beyer, Leonie;Song, Mengmeng;Palleis, Carla;Gehmeyr, Mona;Fietzek, Urban;Respondek, Gesine;Sauerbeck, Julia;Nitschmann, Alexander;Zach, Christian;Hammes, Jochen;Barbe, Michael T;Onur, Oezguer;Jessen, Frank;Saur, Dorothee;Schroeter, Matthias L;Rumpf, Jost-Julian;Rullmann, Michael;Schildan, Andreas;Patt, Marianne;Neumaier, Bernd;Barret, Olivier;Madonia, Jennifer;Russell, David S;Stephens, Andrew;Roeber, Sigrun;Herms, Jochen;Bötzel, Kai;Classen, Joseph;Bartenstein, Peter;Villemagne, Victor L ;Levin, Johannes;Höglinger, Günter U;Drzezga, Alexander;Seibyl, John;Sabri, Osama
Affiliation: Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany
Medicine (University of Melbourne)
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
Department of Neurology, Technical University Munich, Munich, Germany
Department of Neurology, University Hospital of Munich, LMU Munich, Munich, Germany
German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
Center for Neuropathology and Prion Research, University Hospital of Munich, LMU Munich, Munich, Germany
Clinic for Cognitive Neurology, University of Leipzig, Leipzig, Germany
LIFE-Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
Department of Psychiatry, University Hospital Cologne, Cologne, Germany
Center for Memory Disorders, University Hospital Cologne, Cologne, Germany
Department of Neurology, University Hospital Cologne, Cologne, Germany
German Center for Neurodegenerative Diseases (DZNE), Bonn-Cologne, Germany
Molecular Imaging and Therapy
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany
InviCRO LLC, Boston, Massachusetts
Molecular Neuroimaging, A Division of InviCRO, New Haven, Connecticut..
Department of Nuclear Medicine, University Hospital Cologne, Cologne, Germany
German Center for Neurodegenerative Diseases (DZNE), Bonn-Cologne, Germany
Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Jülich, Germany..
Department of Neurology, Hannover Medical School, Hannover, Germany
German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany
Department of Neurology, University Hospital of Munich, LMU Munich, Munich, Germany
Department of Neurology, Hannover Medical School, Hannover, Germany
Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany
Department of Nuclear Medicine, University Hospital Cologne, Cologne, Germany
Department of Neurology, University Hospital Cologne, Cologne, Germany
Department of Neurology, University of Leipzig, Leipzig, Germany
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany
Life Molecular Imaging GmbH, Berlin, Germany..
Center for Neuropathology and Prion Research, University Hospital of Munich, LMU Munich, Munich, Germany..
Department of Neurology, University Hospital of Munich, LMU Munich, Munich, Germany..
Department of Neurology, University of Leipzig, Leipzig, Germany
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany
Issue Date: 1-Nov-2020
metadata.dc.date: 2020-11-01
Publication information: JAMA Neurology 2020; 77(11): 1408-1419
Abstract: 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. To investigate the potential of the novel tau radiotracer 18F-PI-2620 as a biomarker in patients with clinically diagnosed PSP. 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. 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. 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. This multicenter evaluation indicates a value of 18F-PI-2620 to differentiate suspected patients with PSP, potentially facilitating more reliable diagnosis of PSP.
URI: https://ahro.austin.org.au/austinjspui/handle/1/25306
DOI: 10.1001/jamaneurol.2020.2526
PubMed URL: 33165511
Type: Journal Article
Appears in Collections:Journal articles

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