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@ARTICLE{Ballweg:256590,
author = {Ballweg, Anna and Klaus, Carolin and Vogler, Letizia and
Katzdobler, Sabrina and Wind, Karin and Zatcepin, Artem and
Ziegler, Sibylle I and Secgin, Birkan and Eckenweber,
Florian and Bohr, Bernd and Bernhardt, Maximilian Alexander
and Fietzek, Urban and Rauchmann, Boris-Stephan and
Stoecklein, Sophia and Quach, Stefanie and Beyer, Leonie and
Scheifele, Maximilian and Simmet, Marcel and Joseph, Emanuel
and Lindner, Simon and Berg, Isabella and Koglin, Norman and
Mueller, Andre and Stephens, Andrew W and Bartenstein, Peter
and Tonn, Joerg C and Albert, Nathalie L and Kümpfel, Tania
and Kerschensteiner, Martin and Perneczky, Robert and Levin,
Johannes and Paeger, Lars and Herms, Jochen and Brendel,
Matthias},
title = {[18{F}]{F}-{DED} {PET} imaging of reactive astrogliosis in
neurodegenerative diseases: preclinical proof of concept and
first-in-human data.},
journal = {Journal of neuroinflammation},
volume = {20},
number = {1},
issn = {1742-2094},
address = {London},
publisher = {BioMed Central},
reportid = {DZNE-2023-00348},
pages = {68},
year = {2023},
note = {CC BY},
abstract = {Reactive gliosis is a common pathological hallmark of CNS
pathology resulting from neurodegeneration and
neuroinflammation. In this study we investigate the
capability of a novel monoamine oxidase B (MAO-B) PET ligand
to monitor reactive astrogliosis in a transgenic mouse model
of Alzheimer`s disease (AD). Furthermore, we performed a
pilot study in patients with a range of neurodegenerative
and neuroinflammatory conditions.A cross-sectional cohort of
24 transgenic (PS2APP) and 25 wild-type mice (age range:
4.3-21.0 months) underwent 60 min dynamic
[18F]fluorodeprenyl-D2 ([18F]F-DED), static 18 kDa
translocator protein (TSPO, [18F]GE-180) and β-amyloid
([18F]florbetaben) PET imaging. Quantification was performed
via image derived input function (IDIF, cardiac input),
simplified non-invasive reference tissue modelling (SRTM2,
DVR) and late-phase standardized uptake value ratios (SUVr).
Immunohistochemical (IHC) analyses of glial fibrillary
acidic protein (GFAP) and MAO-B were performed to validate
PET imaging by gold standard assessments. Patients belonging
to the Alzheimer's disease continuum (AD, n = 2),
Parkinson's disease (PD, n = 2), multiple system atrophy
(MSA, n = 2), autoimmune encephalitis (n = 1),
oligodendroglioma (n = 1) and one healthy control underwent
60 min dynamic [18F]F-DED PET and the data were analyzed
using equivalent quantification strategies.We selected the
cerebellum as a pseudo-reference region based on the
immunohistochemical comparison of age-matched PS2APP and WT
mice. Subsequent PET imaging revealed that PS2APP mice
showed elevated hippocampal and thalamic [18F]F-DED DVR when
compared to age-matched WT mice at 5 months (thalamus: +
$4.3\%;$ p = 0.048), 13 months (hippocampus: + $7.6\%,$ p =
0.022) and 19 months (hippocampus: + $12.3\%,$ p < 0.0001;
thalamus: + $15.2\%,$ p < 0.0001). Specific [18F]F-DED DVR
increases of PS2APP mice occurred earlier when compared to
signal alterations in TSPO and β-amyloid PET and [18F]F-DED
DVR correlated with quantitative immunohistochemistry
(hippocampus: R = 0.720, p < 0.001; thalamus: R = 0.727, p =
0.002). Preliminary experience in patients showed [18F]F-DED
VT and SUVr patterns, matching the expected topology of
reactive astrogliosis in neurodegenerative (MSA) and
neuroinflammatory conditions, whereas the patient with
oligodendroglioma and the healthy control indicated
[18F]F-DED binding following the known physiological MAO-B
expression in brain.[18F]F-DED PET imaging is a promising
approach to assess reactive astrogliosis in AD mouse models
and patients with neurological diseases.},
keywords = {Humans / Mice / Animals / Infant / Gliosis: pathology /
Neurodegenerative Diseases: metabolism / Oligodendroglioma:
metabolism / Oligodendroglioma: pathology / Cross-Sectional
Studies / Pilot Projects / Alzheimer Disease: pathology /
Positron-Emission Tomography: methods / Amyloid
beta-Peptides: metabolism / Brain: metabolism / Mice,
Transgenic / Inflammation: metabolism / Monoamine Oxidase:
metabolism / Receptors, GABA: metabolism / Astrocytes
(Other) / Deprenyl (Other) / MAO-B (Other) / PET (Other) /
Amyloid beta-Peptides (NLM Chemicals) / Monoamine Oxidase
(NLM Chemicals) / TSPO protein, human (NLM Chemicals) /
Receptors, GABA (NLM Chemicals)},
cin = {AG Haass old / AG Herms / AG Dichgans / Clinical Dementia
Research München},
ddc = {610},
cid = {I:(DE-2719)1110007 / I:(DE-2719)1110001 /
I:(DE-2719)5000022 / I:(DE-2719)1111016},
pnm = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36906584},
pmc = {pmc:PMC10007845},
doi = {10.1186/s12974-023-02749-2},
url = {https://pub.dzne.de/record/256590},
}