학술논문
[18F]F-DED PET imaging of reactive astrogliosis in neurodegenerative diseases: preclinical proof of concept and first-in-human data
Document Type
article
Author
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
Source
Journal of Neuroinflammation, Vol 20, Iss 1, Pp 1-16 (2023)
Subject
Language
English
ISSN
1742-2094
Abstract
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