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000154698 0247_ $$2ISSN$$a0375-8540
000154698 0247_ $$2ISSN$$a1538-3687
000154698 0247_ $$2ISSN$$a2168-6149
000154698 0247_ $$2ISSN$$a2168-6157
000154698 0247_ $$2ISSN$$a2330-9644
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000154698 1001_ $$0P:(DE-HGF)0$$aBrendel, Matthias$$b0$$eCorresponding author
000154698 245__ $$aAssessment of 18F-PI-2620 as a Biomarker in Progressive Supranuclear Palsy.´ment
000154698 260__ $$aChicago, Ill.$$bAmerican Medical Association$$c2020
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000154698 520__ $$aProgressive 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.
000154698 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x0
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000154698 650_7 $$2NLM Chemicals$$a((18)F)PI-2620
000154698 650_7 $$2NLM Chemicals$$aBiomarkers
000154698 650_7 $$2NLM Chemicals$$aFluorine Radioisotopes
000154698 650_7 $$2NLM Chemicals$$aPyridines
000154698 650_7 $$2NLM Chemicals$$atau Proteins
000154698 650_2 $$2MeSH$$aAged
000154698 650_2 $$2MeSH$$aBiomarkers: metabolism
000154698 650_2 $$2MeSH$$aCross-Sectional Studies
000154698 650_2 $$2MeSH$$aDiagnosis
000154698 650_2 $$2MeSH$$aFemale
000154698 650_2 $$2MeSH$$aFluorine Radioisotopes: pharmacokinetics
000154698 650_2 $$2MeSH$$aGray Matter: diagnostic imaging
000154698 650_2 $$2MeSH$$aGray Matter: metabolism
000154698 650_2 $$2MeSH$$aHumans
000154698 650_2 $$2MeSH$$aMale
000154698 650_2 $$2MeSH$$aMiddle Aged
000154698 650_2 $$2MeSH$$aMultiple System Atrophy: diagnostic imaging
000154698 650_2 $$2MeSH$$aMultiple System Atrophy: metabolism
000154698 650_2 $$2MeSH$$aParkinson Disease: diagnostic imaging
000154698 650_2 $$2MeSH$$aParkinson Disease: metabolism
000154698 650_2 $$2MeSH$$aPositron-Emission Tomography: standards
000154698 650_2 $$2MeSH$$aPyridines: pharmacokinetics
000154698 650_2 $$2MeSH$$aSensitivity and Specificity
000154698 650_2 $$2MeSH$$aSeverity of Illness Index
000154698 650_2 $$2MeSH$$aSupranuclear Palsy, Progressive: diagnostic imaging
000154698 650_2 $$2MeSH$$aSupranuclear Palsy, Progressive: metabolism
000154698 650_2 $$2MeSH$$atau Proteins: metabolism
000154698 7001_ $$aBarthel, Henryk$$b1
000154698 7001_ $$0P:(DE-HGF)0$$avan Eimeren, Thilo$$b2
000154698 7001_ $$0P:(DE-HGF)0$$aMarek, Ken$$b3
000154698 7001_ $$aSong, Mengmeng$$b4
000154698 7001_ $$0P:(DE-HGF)0$$aPalleis, Carla$$b5
000154698 7001_ $$0P:(DE-HGF)0$$aGehmeyr, Mona$$b6
000154698 7001_ $$aBeyer, Leonie$$b7
000154698 7001_ $$0P:(DE-HGF)0$$aFietzek, Urban$$b8
000154698 7001_ $$0P:(DE-HGF)0$$aRespondek, Gesine$$b9
000154698 7001_ $$aSauerbeck, Julia$$b10
000154698 7001_ $$aNitschmann, Alexander$$b11
000154698 7001_ $$aZach, Christian$$b12
000154698 7001_ $$aHammes, Jochen$$b13
000154698 7001_ $$aBarbe, Michael T$$b14
000154698 7001_ $$aOnur, Oezguer$$b15
000154698 7001_ $$0P:(DE-2719)2000032$$aJessen, Frank$$b16
000154698 7001_ $$aSaur, Dorothee$$b17
000154698 7001_ $$aSchroeter, Matthias L$$b18
000154698 7001_ $$aRumpf, Jost-Julian$$b19
000154698 7001_ $$aRullmann, Michael$$b20
000154698 7001_ $$aSchildan, Andreas$$b21
000154698 7001_ $$aPatt, Marianne$$b22
000154698 7001_ $$aNeumaier, Bernd$$b23
000154698 7001_ $$aBarret, Olivier$$b24
000154698 7001_ $$aMadonia, Jennifer$$b25
000154698 7001_ $$aRussell, David S$$b26
000154698 7001_ $$aStephens, Andrew$$b27
000154698 7001_ $$aRoeber, Sigrun$$b28
000154698 7001_ $$0P:(DE-2719)2810441$$aHerms, Jochen$$b29
000154698 7001_ $$aBötzel, Kai$$b30
000154698 7001_ $$aClassen, Joseph$$b31
000154698 7001_ $$aBartenstein, Peter$$b32
000154698 7001_ $$aVillemagne, Victor$$b33
000154698 7001_ $$0P:(DE-2719)2811659$$aLevin, Johannes$$b34
000154698 7001_ $$0P:(DE-2719)2811373$$aHöglinger, Günter$$b35
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000154698 7001_ $$aSeibyl, John$$b37
000154698 7001_ $$0P:(DE-HGF)0$$aSabri, Osama$$b38
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