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  Assessment of18F-PI-2620 as a biomarker in progressive supranuclear palsy

Brendel, M., Barthel, H., van Eimeren, T., Marek, K., Beyer, L., Song, M., et al. (2020). Assessment of18F-PI-2620 as a biomarker in progressive supranuclear palsy. JAMA Neurology, 77(11), 1408-1419. doi:10.1001/jamaneurol.2020.2526.

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 Creators:
Brendel, Matthias1, Author
Barthel, Henryk1, Author
van Eimeren, Thilo1, Author
Marek, Ken1, Author
Beyer, Leonie1, Author
Song, Mengmeng1, Author
Palleis, Carla1, Author
Gehmeyr, Mona1, Author
Fietzek, Urban1, Author
Respondek, Gesine1, Author
Sauerbeck, Julia1, Author
Nitschmann, Alexander1, Author
Zach, Christian1, Author
Hammes, Jochen1, Author
Barbe, Michael T.1, Author
Onur, Oezguer1, Author
Jessen, Frank1, Author
Saur, Dorothee1, Author
Schroeter, Matthias L.2, Author              
Rumpf, Jost-Julian1, Author
Rullmann, Michael1, AuthorSchildan, Andreas1, AuthorPatt, Marianne1, AuthorNeumaier, Bernd1, AuthorBarret, Olivier1, AuthorMadonia, Jennifer1, AuthorRussell, David S.1, AuthorStephens, Andrew1, AuthorRoeber, Sigrun1, AuthorHerms, Jochen1, AuthorBötzel, Kai1, AuthorClassen, Joseph1, AuthorBartenstein, Peter1, AuthorVillemagne, Victor1, AuthorLevin, Johannes1, AuthorHöglinger, Günter U.1, AuthorDrzezga, Alexander1, AuthorSeibyl, John1, AuthorSabri, Osama1, Author more..
Affiliations:
1External Organizations, ou_persistent22              
2Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              

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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 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.

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Language(s): eng - English
 Dates: 2020-05-012020-07-072020-11-01
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1001/jamaneurol.2020.2526
PMID: 33165511
PMC: PMC7341407
 Degree: -

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Grant ID : 390857198
Funding program : Munich Cluster for Systems Neurology
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Title: JAMA Neurology
  Abbreviation : JAMA Neurol
Source Genre: Journal
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Publ. Info: Chicago, Ill. : American Medical Association
Pages: - Volume / Issue: 77 (11) Sequence Number: - Start / End Page: 1408 - 1419 Identifier: Other: 2168-6157
CoNE: https://pure.mpg.de/cone/journals/resource/2168-6157