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@ARTICLE{Willroider:155694,
author = {Willroider, Marie and Roeber, Sigrun and Horn, Anja K E and
Arzberger, Thomas and Scheifele, Heinrich Maximilian and
Respondek, Gesine and Sabri, Osama and Barthel, Henryk and
Patt, Marianne and Mishchenko, Olena and Schildan, Andreas
and Mueller, André and Koglin, Norman and Stephens, Andrew
and Levin, Johannes and Höglinger, Günter U and
Bartenstein, Peter and Herms, Jochen and Brendel, Matthias
and Beyer, Leonie},
title = {{S}uperiority of {F}ormalin-{F}ixed {P}araffin-{E}mbedded
{B}rain {T}issue for in vitro {A}ssessment of {P}rogressive
{S}upranuclear {P}alsy {T}au {P}athology {W}ith [ 18
{F}]{PI}-2620.},
journal = {Frontiers in neurology},
volume = {12},
issn = {1664-2295},
address = {Lausanne},
publisher = {Frontiers Research Foundation},
reportid = {DZNE-2021-00862},
pages = {684523},
year = {2021},
abstract = {Objectives: Autoradiography on brain tissue is used to
validate binding targets of newly discovered radiotracers.
The purpose of this study was to correlate quantification of
autoradiography signal using the novel next-generation tau
positron emission tomography (PET) radiotracer [18F]PI-2620
with immunohistochemically determined tau-protein load in
both formalin-fixed paraffin-embedded (FFPE) and frozen
tissue samples of patients with Alzheimer's disease (AD) and
Progressive Supranuclear Palsy (PSP). Methods: We applied
[18F]PI-2620 autoradiography to postmortem cortical brain
samples of six patients with AD, five patients with PSP and
five healthy controls, respectively. Binding intensity was
compared between both tissue types and different disease
entities. Autoradiography signal quantification (CWMR =
cortex to white matter ratio) was correlated with the
immunohistochemically assessed tau load (AT8-staining,
$\%-area)$ for FFPE and frozen tissue samples in the
different disease entities. Results: In AD tissue, relative
cortical tracer binding was higher in frozen samples when
compared to FFPE samples (CWMRfrozen vs. CWMRFFPE: 2.5-fold,
p < 0.001), whereas the opposite was observed in PSP tissue
(CWMRfrozen vs. CWMRFFPE: 0.8-fold, p = 0.004). In FFPE
samples, [18F]PI-2620 autoradiography tracer binding and
immunohistochemical tau load correlated significantly for
both PSP (R = 0.641, p < 0.001) and AD tissue (R = 0.435, p
= 0.016), indicating a high agreement of relative tracer
binding with underlying pathology. In frozen tissue, the
correlation between autoradiography and immunohistochemistry
was only present in AD (R = 0.417, p = 0.014) but not in PSP
tissue (R = -0.115, p = n.s.). Conclusion: Our head-to-head
comparison indicates that FFPE samples show superiority over
frozen samples for autoradiography assessment of PSP tau
pathology by [18F]PI-2620. The [18F]PI-2620 autoradiography
signal in FFPE samples reflects AT8 positive tau in samples
of both PSP and AD patients.},
keywords = {PI-2620 (Other) / autoradiography (Other) /
immunohistochemistry (Other) / progressive supranuclear
palsy (Other) / tau (Other)},
cin = {Neuropathology / Brainbank / Clinical Research (Munich) /
AG Herms / AG Levin},
ddc = {610},
cid = {I:(DE-2719)1140013 / I:(DE-2719)1111015 /
I:(DE-2719)1110001 / I:(DE-2719)1111016},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 352 -
Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34276540},
pmc = {pmc:PMC8282895},
doi = {10.3389/fneur.2021.684523},
url = {https://pub.dzne.de/record/155694},
}