[18F]F-DED PET imaging of reactive astrogliosis in neurodegenerative diseases: preclinical proof of concept and first-in-human data

Autor: Anna Ballweg, Carolin Klaus, Letizia Vogler, Sabrina Katzdobler, Karin Wind, Artem Zatcepin, Sibylle I. Ziegler, Birkan Secgin, Florian Eckenweber, Bernd Bohr, Alexander Bernhardt, Urban Fietzek, Boris-Stephan Rauchmann, Sophia Stoecklein, Stefanie Quach, Leonie Beyer, Maximilian Scheifele, Marcel Simmet, Emanuel Joseph, Simon Lindner, Isabella Berg, Norman Koglin, Andre Mueller, Andrew W. Stephens, Peter Bartenstein, Joerg C. Tonn, Nathalie L. Albert, Tania Kümpfel, Martin Kerschensteiner, Robert Perneczky, Johannes Levin, Lars Paeger, Jochen Herms, Matthias Brendel
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Neuroinflammation, Vol 20, Iss 1, Pp 1-16 (2023)
Druh dokumentu: article
ISSN: 1742-2094
DOI: 10.1186/s12974-023-02749-2
Popis: Abstract Objectives 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. Methods 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. Results 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
Databáze: Directory of Open Access Journals
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