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 ORCID: 0000-0002-1808-0913, 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, Boetzel, Kai, Classen, Joseph, Bartenstein, Peter, Villemagne, Victor, Levin, Johannes, Hoeglinger, Guenter U., Drzezga, Alexander, Seibyl, John and Sabri, Osama (2020). Assessment of F-18-PI-2620 as a Biomarker in Progressive Supranuclear Palsy. JAMA Neurol., 77 (11). S. 1408 - 1420. CHICAGO: AMER MEDICAL ASSOC. ISSN 2168-6157

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Abstract

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 F-18-PI-2620 as a biomarker in patients with clinically diagnosed PSP. Design, Setting, and Participants In this cross-sectional study, participants underwent dynamic F-18-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, F-18-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 F-18-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 F-18-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 F-18-PI-2620 to differentiate suspected patients with PSP, potentially facilitating more reliable diagnosis of PSP. Question Can tau-positron emission tomography imaging with the novel tau radiotracer F-18-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 F-18-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 F-18-PI-2620 tau-positron emission tomography differentiates patients with PSP from controls at the single-patient level, potentially facilitating a more reliable diagnosis. This cross-sectional study investigates the potential of novel tau radiotracer F-18-PI-2620 as a biomarker in patients with clinically diagnosed progressive supranuclear palsy.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Brendel, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barthel, HenrykUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Eimeren, ThiloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marek, KenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beyer, LeonieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Song, MengmengUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Palleis, CarlaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gehmeyr, MonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fietzek, UrbanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Respondek, GesineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sauerbeck, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nitschmann, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zach, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hammes, JochenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barbe, Michael T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Onur, OezguerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jessen, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saur, DorotheeUNSPECIFIEDorcid.org/0000-0002-1808-0913UNSPECIFIED
Schroeter, Matthias L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rumpf, Jost-JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rullmann, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schildan, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Patt, MarianneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neumaier, BerndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barret, OlivierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Madonia, JenniferUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Russell, David S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stephens, AndrewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roeber, SigrunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herms, JochenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boetzel, KaiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Classen, JosephUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bartenstein, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Villemagne, VictorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Levin, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoeglinger, Guenter U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drzezga, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seibyl, JohnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sabri, OsamaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-312648
DOI: 10.1001/jamaneurol.2020.2526
Journal or Publication Title: JAMA Neurol.
Volume: 77
Number: 11
Page Range: S. 1408 - 1420
Date: 2020
Publisher: AMER MEDICAL ASSOC
Place of Publication: CHICAGO
ISSN: 2168-6157
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
POSITRON-EMISSION-TOMOGRAPHY; DIAGNOSTIC-CRITERIA; ALZHEIMERS-DISEASE; BRAIN; ATLASMultiple languages
Clinical NeurologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/31264

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