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@ARTICLE{Brendel:889144,
author = {Brendel, Matthias and Barthel, Henryk and van Eimeren,
Thilo and Marek, Ken and Beyer, Leonie and Song, Mengmeng
and Palleis, Carla and Gehmeyr, Mona and Fietzek, Urban and
Respondek, Gesine and Sauerbeck, Julia and Nitschmann,
Alexander and Zach, Christian and Hammes, Jochen and Barbe,
Michael T. and Onur, Oezguer and Jessen, Frank and Saur,
Dorothee and Schroeter, Matthias L. and Rumpf, Jost-Julian
and Rullmann, Michael and Schildan, Andreas and Patt,
Marianne and Neumaier, Bernd and Barret, Olivier and
Madonia, Jennifer and Russell, David S. and Stephens, Andrew
and Roeber, Sigrun and Herms, Jochen and Bötzel, Kai and
Classen, Joseph and Bartenstein, Peter and Villemagne,
Victor and Levin, Johannes and Höglinger, Günter U. and
Drzezga, Alexander and Seibyl, John and Sabri, Osama},
title = {{A}ssessment of 18 {F}-{PI}-2620 as a {B}iomarker in
{P}rogressive {S}upranuclear {P}alsy},
journal = {JAMA neurology},
volume = {77},
number = {11},
issn = {2168-6149},
address = {Chicago, Ill.},
publisher = {American Medical Association},
reportid = {FZJ-2021-00069},
pages = {1408 -},
year = {2020},
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.},
cin = {INM-2 / INM-5},
ddc = {610},
cid = {I:(DE-Juel1)INM-2-20090406 / I:(DE-Juel1)INM-5-20090406},
pnm = {572 - (Dys-)function and Plasticity (POF3-572) / 573 -
Neuroimaging (POF3-573)},
pid = {G:(DE-HGF)POF3-572 / G:(DE-HGF)POF3-573},
typ = {PUB:(DE-HGF)16},
pubmed = {33165511},
UT = {WOS:000593760500013},
doi = {10.1001/jamaneurol.2020.2526},
url = {https://juser.fz-juelich.de/record/889144},
}