Advanced MRI Center, Department of Radiology
Nervous System Diseases | Neuroscience and Neurobiology | Radiology
BACKGROUND: Positron emission tomography (PET) using translocator protein (TSPO) ligands has been used to detect neuroinflammatory processes in neurological disorders, including multiple sclerosis (MS). The aim of this study was to evaluate neuroinflammation in a mouse MS model (EAE) using TSPO-PET with (18)F-VC701, in combination with magnetic resonance imaging (MRI).
METHODS: MOG35-55/CFA and pertussis toxin protocol was used to induce EAE in C57BL/6 mice. Disease progression was monitored daily, whereas MRI evaluation was performed at 1, 2, and 4 weeks post-induction. Microglia activation was assessed in vivo by (18)F-VC701 PET at the time of maximum disease score and validated by radioligand ex vivo distribution and immunohistochemistry at 2 and 4 weeks post-immunization.
RESULTS: In vivo and ex vivo analyses show that (18)F-VC701 significantly accumulates within the central nervous system (CNS), particularly in the cortex, striatum, hippocampus, cerebellum, and cervical spinal cord of EAE compared to control mice, at 2 weeks post-immunization. MRI confirmed the presence of focal brain lesions at 2 weeks post-immunization in both T1-weighted and T2 images. Of note, MRI abnormalities attenuated in later post-immunization phase. Neuropathological analysis confirmed the presence of microglial activation in EAE mice, consistent with the in vivo increase of (18)F-VC701 uptake.
CONCLUSION: Increase of (18)F-VC701 uptake in EAE mice is strongly associated with the presence of microglia activation in the acute phase of the disease. The combined use of TSPO-PET and MRI provided complementary evidence on the ongoing disease process, thus representing an attractive new tool to investigate neuronal damage and neuroinflammation at preclinical levels.
EAE monophasic model, MRI, Multiple sclerosis, Neuroinflammation, TSPO-PET
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© The Author(s). 2018. Open Access.This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
DOI of Published Version
J Neuroinflammation. 2018 Feb 5;15(1):33. doi: 10.1186/s12974-017-1044-x. Link to article on publisher's site
Journal of neuroinflammation
Belloli, Sara; Zanotti, Lucia; Murtaj, Valentina; Mazzon, Cristina; Di Grigoli, Giuseppe; Monterisi, Cristina; Masiello, Valeria; Iaccarino, Leonardo; Cappelli, Andrea; Poliani, Pietro Luigi; Politi, Letterio S.; and Moresco, Rosa Maria, "(18)F-VC701-PET and MRI in the in vivo neuroinflammation assessment of a mouse model of multiple sclerosis" (2018). Radiology Publications and Presentations. 382.
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This work is licensed under a Creative Commons Attribution 4.0 License.