Home > Publications Database > [18F]F-DED PET imaging of reactive astrogliosis in neurodegenerative diseases: preclinical proof of concept and first-in-human data. > print

001     256590
005     20231120155337.0
024 7 _ |a pmid:36906584
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024 7 _ |a pmc:PMC10007845
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024 7 _ |a 10.1186/s12974-023-02749-2
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037 _ _ |a DZNE-2023-00348
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Ballweg, Anna
|b 0
245 _ _ |a [18F]F-DED PET imaging of reactive astrogliosis in neurodegenerative diseases: preclinical proof of concept and first-in-human data.
260 _ _ |a London
|c 2023
|b BioMed Central
336 7 _ |a article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a JOURNAL_ARTICLE
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336 7 _ |a Journal Article
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500 _ _ |a CC BY
520 _ _ |a 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.
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650 _ 7 |a Astrocytes
|2 Other
650 _ 7 |a Deprenyl
|2 Other
650 _ 7 |a MAO-B
|2 Other
650 _ 7 |a PET
|2 Other
650 _ 7 |a Amyloid beta-Peptides
|2 NLM Chemicals
650 _ 7 |a Monoamine Oxidase
|0 EC 1.4.3.4
|2 NLM Chemicals
650 _ 7 |a TSPO protein, human
|2 NLM Chemicals
650 _ 7 |a Receptors, GABA
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Infant
|2 MeSH
650 _ 2 |a Gliosis: pathology
|2 MeSH
650 _ 2 |a Neurodegenerative Diseases: metabolism
|2 MeSH
650 _ 2 |a Oligodendroglioma: metabolism
|2 MeSH
650 _ 2 |a Oligodendroglioma: pathology
|2 MeSH
650 _ 2 |a Cross-Sectional Studies
|2 MeSH
650 _ 2 |a Pilot Projects
|2 MeSH
650 _ 2 |a Alzheimer Disease: pathology
|2 MeSH
650 _ 2 |a Positron-Emission Tomography: methods
|2 MeSH
650 _ 2 |a Amyloid beta-Peptides: metabolism
|2 MeSH
650 _ 2 |a Brain: metabolism
|2 MeSH
650 _ 2 |a Mice, Transgenic
|2 MeSH
650 _ 2 |a Inflammation: metabolism
|2 MeSH
650 _ 2 |a Monoamine Oxidase: metabolism
|2 MeSH
650 _ 2 |a Receptors, GABA: metabolism
|2 MeSH
700 1 _ |a Klaus, Carolin
|0 P:(DE-2719)9001221
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700 1 _ |a Vogler, Letizia
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700 1 _ |a Katzdobler, Sabrina
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700 1 _ |a Wind, Karin
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700 1 _ |a Zatcepin, Artem
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700 1 _ |a Ziegler, Sibylle I
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700 1 _ |a Secgin, Birkan
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700 1 _ |a Eckenweber, Florian
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700 1 _ |a Bohr, Bernd
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700 1 _ |a Bernhardt, Maximilian Alexander
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700 1 _ |a Fietzek, Urban
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700 1 _ |a Rauchmann, Boris-Stephan
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700 1 _ |a Stoecklein, Sophia
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700 1 _ |a Quach, Stefanie
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700 1 _ |a Beyer, Leonie
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700 1 _ |a Scheifele, Maximilian
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700 1 _ |a Simmet, Marcel
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700 1 _ |a Joseph, Emanuel
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700 1 _ |a Lindner, Simon
|b 19
700 1 _ |a Berg, Isabella
|b 20
700 1 _ |a Koglin, Norman
|b 21
700 1 _ |a Mueller, Andre
|b 22
700 1 _ |a Stephens, Andrew W
|b 23
700 1 _ |a Bartenstein, Peter
|b 24
700 1 _ |a Tonn, Joerg C
|b 25
700 1 _ |a Albert, Nathalie L
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700 1 _ |a Kümpfel, Tania
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700 1 _ |a Kerschensteiner, Martin
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700 1 _ |a Perneczky, Robert
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700 1 _ |a Levin, Johannes
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700 1 _ |a Paeger, Lars
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700 1 _ |a Herms, Jochen
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700 1 _ |a Brendel, Matthias
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773 _ _ |a 10.1186/s12974-023-02749-2
|g Vol. 20, no. 1
|0 PERI:(DE-600)2156455-3
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|p 68
|t Journal of neuroinflammation
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|x 1742-2094
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