| First Author | Ballweg A | Year | 2023 |
| Journal | J Neuroinflammation | Volume | 20 |
| Issue | 1 | Pages | 68 |
| PubMed ID | 36906584 | Mgi Jnum | J:339796 |
| Mgi Id | MGI:7445849 | Doi | 10.1186/s12974-023-02749-2 |
| Citation | Ballweg A, et al. (2023) [(18)F]F-DED PET imaging of reactive astrogliosis in neurodegenerative diseases: preclinical proof of concept and first-in-human data. J Neuroinflammation 20(1):68 |
| abstractText | 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 [(18)F]fluorodeprenyl-D2 ([(18)F]F-DED), static 18 kDa translocator protein (TSPO, [(18)F]GE-180) and beta-amyloid ([(18)F]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 [(18)F]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 [(18)F]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 [(18)F]F-DED DVR increases of PS2APP mice occurred earlier when compared to signal alterations in TSPO and beta-amyloid PET and [(18)F]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 [(18)F]F-DED V(T) 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 [(18)F]F-DED binding following the known physiological MAO-B expression in brain. CONCLUSIONS: [(18)F]F-DED PET imaging is a promising approach to assess reactive astrogliosis in AD mouse models and patients with neurological diseases. |
