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024 7 _ |a 10.1001/jamaneurol.2020.2526
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024 7 _ |a 0375-8540
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024 7 _ |a 1538-3687
|2 ISSN
024 7 _ |a 2168-6149
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024 7 _ |a 2168-6157
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024 7 _ |a 2330-9644
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037 _ _ |a DZNE-2021-00307
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Brendel, Matthias
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|e Corresponding author
245 _ _ |a Assessment of 18F-PI-2620 as a Biomarker in Progressive Supranuclear Palsy.´ment
260 _ _ |a Chicago, Ill.
|c 2020
|b American Medical Association
336 7 _ |a article
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520 _ _ |a 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.
536 _ _ |a 344 - Clinical and Health Care Research (POF3-344)
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|c POF3-344
|f POF III
|x 0
536 _ _ |a 342 - Disease Mechanisms and Model Systems (POF3-342)
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588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a ((18)F)PI-2620
|2 NLM Chemicals
650 _ 7 |a Biomarkers
|2 NLM Chemicals
650 _ 7 |a Fluorine Radioisotopes
|2 NLM Chemicals
650 _ 7 |a Pyridines
|2 NLM Chemicals
650 _ 7 |a tau Proteins
|2 NLM Chemicals
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Biomarkers: metabolism
|2 MeSH
650 _ 2 |a Cross-Sectional Studies
|2 MeSH
650 _ 2 |a Diagnosis
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Fluorine Radioisotopes: pharmacokinetics
|2 MeSH
650 _ 2 |a Gray Matter: diagnostic imaging
|2 MeSH
650 _ 2 |a Gray Matter: metabolism
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Multiple System Atrophy: diagnostic imaging
|2 MeSH
650 _ 2 |a Multiple System Atrophy: metabolism
|2 MeSH
650 _ 2 |a Parkinson Disease: diagnostic imaging
|2 MeSH
650 _ 2 |a Parkinson Disease: metabolism
|2 MeSH
650 _ 2 |a Positron-Emission Tomography: standards
|2 MeSH
650 _ 2 |a Pyridines: pharmacokinetics
|2 MeSH
650 _ 2 |a Sensitivity and Specificity
|2 MeSH
650 _ 2 |a Severity of Illness Index
|2 MeSH
650 _ 2 |a Supranuclear Palsy, Progressive: diagnostic imaging
|2 MeSH
650 _ 2 |a Supranuclear Palsy, Progressive: metabolism
|2 MeSH
650 _ 2 |a tau Proteins: metabolism
|2 MeSH
700 1 _ |a Barthel, Henryk
|b 1
700 1 _ |a van Eimeren, Thilo
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700 1 _ |a Marek, Ken
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700 1 _ |a Song, Mengmeng
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700 1 _ |a Palleis, Carla
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700 1 _ |a Gehmeyr, Mona
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700 1 _ |a Beyer, Leonie
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700 1 _ |a Fietzek, Urban
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700 1 _ |a Respondek, Gesine
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700 1 _ |a Sauerbeck, Julia
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700 1 _ |a Nitschmann, Alexander
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700 1 _ |a Zach, Christian
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700 1 _ |a Hammes, Jochen
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700 1 _ |a Barbe, Michael T
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700 1 _ |a Onur, Oezguer
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700 1 _ |a Jessen, Frank
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700 1 _ |a Saur, Dorothee
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700 1 _ |a Schroeter, Matthias L
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700 1 _ |a Rumpf, Jost-Julian
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700 1 _ |a Rullmann, Michael
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700 1 _ |a Schildan, Andreas
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700 1 _ |a Patt, Marianne
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700 1 _ |a Neumaier, Bernd
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700 1 _ |a Barret, Olivier
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700 1 _ |a Madonia, Jennifer
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700 1 _ |a Russell, David S
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700 1 _ |a Stephens, Andrew
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700 1 _ |a Roeber, Sigrun
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700 1 _ |a Herms, Jochen
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700 1 _ |a Bötzel, Kai
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700 1 _ |a Classen, Joseph
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700 1 _ |a Bartenstein, Peter
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700 1 _ |a Villemagne, Victor
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700 1 _ |a Levin, Johannes
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700 1 _ |a Höglinger, Günter
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700 1 _ |a Drzezga, Alexander
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700 1 _ |a Seibyl, John
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700 1 _ |a Sabri, Osama
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