Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/25306
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dc.contributor.authorBrendel, Matthias-
dc.contributor.authorBarthel, Henryk-
dc.contributor.authorvan Eimeren, Thilo-
dc.contributor.authorMarek, Ken-
dc.contributor.authorBeyer, Leonie-
dc.contributor.authorSong, Mengmeng-
dc.contributor.authorPalleis, Carla-
dc.contributor.authorGehmeyr, Mona-
dc.contributor.authorFietzek, Urban-
dc.contributor.authorRespondek, Gesine-
dc.contributor.authorSauerbeck, Julia-
dc.contributor.authorNitschmann, Alexander-
dc.contributor.authorZach, Christian-
dc.contributor.authorHammes, Jochen-
dc.contributor.authorBarbe, Michael T-
dc.contributor.authorOnur, Oezguer-
dc.contributor.authorJessen, Frank-
dc.contributor.authorSaur, Dorothee-
dc.contributor.authorSchroeter, Matthias L-
dc.contributor.authorRumpf, Jost-Julian-
dc.contributor.authorRullmann, Michael-
dc.contributor.authorSchildan, Andreas-
dc.contributor.authorPatt, Marianne-
dc.contributor.authorNeumaier, Bernd-
dc.contributor.authorBarret, Olivier-
dc.contributor.authorMadonia, Jennifer-
dc.contributor.authorRussell, David S-
dc.contributor.authorStephens, Andrew-
dc.contributor.authorRoeber, Sigrun-
dc.contributor.authorHerms, Jochen-
dc.contributor.authorBötzel, Kai-
dc.contributor.authorClassen, Joseph-
dc.contributor.authorBartenstein, Peter-
dc.contributor.authorVillemagne, Victor L-
dc.contributor.authorLevin, Johannes-
dc.contributor.authorHöglinger, Günter U-
dc.contributor.authorDrzezga, Alexander-
dc.contributor.authorSeibyl, John-
dc.contributor.authorSabri, Osama-
dc.date2020-11-01-
dc.date.accessioned2020-11-19T23:22:13Z-
dc.date.available2020-11-19T23:22:13Z-
dc.date.issued2020-11-01-
dc.identifier.citationJAMA Neurology 2020; 77(11): 1408-1419en
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/25306-
dc.description.abstractProgressive 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.en
dc.language.isoeng
dc.titleAssessment of 18F-PI-2620 as a Biomarker in Progressive Supranuclear Palsy.en
dc.typeJournal Articleen
dc.identifier.journaltitleJAMA Neurologyen
dc.identifier.affiliationDepartment of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germanyen
dc.identifier.affiliationLife Molecular Imaging GmbH, Berlin, Germanyen
dc.identifier.affiliationForschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Jülich, Germanyen
dc.identifier.affiliationCenter for Neuropathology and Prion Research, University Hospital of Munich, LMU Munich, Munich, Germanyen
dc.identifier.affiliationDepartment of Neurology, University Hospital of Munich, LMU Munich, Munich, Germanyen
dc.identifier.affiliationMedicine (University of Melbourne)en
dc.identifier.affiliationMunich Cluster for Systems Neurology (SyNergy), Munich, Germanyen
dc.identifier.affiliationDepartment of Neurology, Technical University Munich, Munich, Germanyen
dc.identifier.affiliationDepartment of Neurology, University Hospital of Munich, LMU Munich, Munich, Germanyen
dc.identifier.affiliationGerman Center for Neurodegenerative Diseases (DZNE), Munich, Germanyen
dc.identifier.affiliationDepartment of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germanyen
dc.identifier.affiliationMunich Cluster for Systems Neurology (SyNergy), Munich, Germanyen
dc.identifier.affiliationCenter for Neuropathology and Prion Research, University Hospital of Munich, LMU Munich, Munich, Germanyen
dc.identifier.affiliationClinic for Cognitive Neurology, University of Leipzig, Leipzig, Germanyen
dc.identifier.affiliationLIFE-Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germanyen
dc.identifier.affiliationMax Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germanyen
dc.identifier.affiliationDepartment of Psychiatry, University Hospital Cologne, Cologne, Germanyen
dc.identifier.affiliationCenter for Memory Disorders, University Hospital Cologne, Cologne, Germanyen
dc.identifier.affiliationDepartment of Neurology, University Hospital Cologne, Cologne, Germanyen
dc.identifier.affiliationGerman Center for Neurodegenerative Diseases (DZNE), Bonn-Cologne, Germanyen
dc.identifier.affiliationMolecular Imaging and Therapyen
dc.identifier.affiliationDepartment of Nuclear Medicine, University of Leipzig, Leipzig, Germanyen
dc.identifier.affiliationInviCRO LLC, Boston, Massachusettsen
dc.identifier.affiliationMolecular Neuroimaging, A Division of InviCRO, New Haven, Connecticut..en
dc.identifier.affiliationDepartment of Nuclear Medicine, University Hospital Cologne, Cologne, Germanyen
dc.identifier.affiliationGerman Center for Neurodegenerative Diseases (DZNE), Bonn-Cologne, Germanyen
dc.identifier.affiliationDepartment of Neurology, Hannover Medical School, Hannover, Germanyen
dc.identifier.affiliationGerman Center for Neurodegenerative Diseases (DZNE), Munich, Germanyen
dc.identifier.affiliationDepartment of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germanyen
dc.identifier.affiliationDepartment of Neurology, University Hospital of Munich, LMU Munich, Munich, Germanyen
dc.identifier.affiliationDepartment of Neurology, Hannover Medical School, Hannover, Germanyen
dc.identifier.affiliationDepartment of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germanyen
dc.identifier.affiliationDepartment of Nuclear Medicine, University Hospital Cologne, Cologne, Germanyen
dc.identifier.affiliationDepartment of Neurology, University Hospital Cologne, Cologne, Germanyen
dc.identifier.affiliationDepartment of Neurology, University of Leipzig, Leipzig, Germanyen
dc.identifier.affiliationDepartment of Nuclear Medicine, University of Leipzig, Leipzig, Germanyen
dc.identifier.affiliationDepartment of Neurology, University of Leipzig, Leipzig, Germanyen
dc.identifier.affiliationDepartment of Nuclear Medicine, University of Leipzig, Leipzig, Germanyen
dc.identifier.doi10.1001/jamaneurol.2020.2526en
dc.type.contentTexten
dc.identifier.pubmedid33165511
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