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@ARTICLE{Brendel:154698,
author = {Brendel, Matthias and Barthel, Henryk and van Eimeren,
Thilo and Marek, Ken and Song, Mengmeng and Palleis, Carla
and Gehmeyr, Mona and Beyer, Leonie 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 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.´ment},
journal = {JAMA neurology},
volume = {77},
number = {11},
issn = {2168-6149},
address = {Chicago, Ill.},
publisher = {American Medical Association},
reportid = {DZNE-2021-00307},
pages = {1408 -},
year = {2020},
abstract = {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.},
keywords = {Aged / Biomarkers: metabolism / Cross-Sectional Studies /
Diagnosis / Female / Fluorine Radioisotopes:
pharmacokinetics / Gray Matter: diagnostic imaging / Gray
Matter: metabolism / Humans / Male / Middle Aged / Multiple
System Atrophy: diagnostic imaging / Multiple System
Atrophy: metabolism / Parkinson Disease: diagnostic imaging
/ Parkinson Disease: metabolism / Positron-Emission
Tomography: standards / Pyridines: pharmacokinetics /
Sensitivity and Specificity / Severity of Illness Index /
Supranuclear Palsy, Progressive: diagnostic imaging /
Supranuclear Palsy, Progressive: metabolism / tau Proteins:
metabolism / ((18)F)PI-2620 (NLM Chemicals) / Biomarkers
(NLM Chemicals) / Fluorine Radioisotopes (NLM Chemicals) /
Pyridines (NLM Chemicals) / tau Proteins (NLM Chemicals)},
cin = {Clinical Dementia Research München / AG Jessen / AG Herms
/ AG Höglinger 2 / AG Boecker},
ddc = {610},
cid = {I:(DE-2719)1111016 / I:(DE-2719)1011102 /
I:(DE-2719)1110001 / I:(DE-2719)1111015 /
I:(DE-2719)1011202},
pnm = {344 - Clinical and Health Care Research (POF3-344) / 342 -
Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-344 / G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33165511},
pmc = {pmc:PMC7341407},
doi = {10.1001/jamaneurol.2020.2526},
url = {https://pub.dzne.de/record/154698},
}