18F-VC701-PET and MRI in the in vivo neuroinflammation assessment of a mouse model of multiple sclerosis

Abstract

BackgroundPositron 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 18F-VC701, in combination with magnetic resonance imaging (MRI).MethodsMOG35-55/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 18F-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.ResultsIn vivo and ex vivo analyses show that 18F-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 18F-VC701 uptake.ConclusionIncrease of 18F-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.Electronic supplementary materialThe online version of this article (10.1186/s12974-017-1044-x) contains supplementary material, which is available to authorized users.

Effect of Methionine Diet on Metabolic and Histopathological Changes of Rat Hippocampus

“…Similar to our previous study, results in this paper clearly determined morphological changes in the neurons and elevation in glia cellularity in Met treated animals. We observed histo-morphological changes such as swelling of neuronal cell bodies linked with the dysregulation of metabolic ratio (decrease in tNAA/tCr and increase in tCho/tCr) and changes in the volumetric analysis which is consonant to the previous studies from different laboratories [40,41] and clinical studies [18,42]. This indicates that different types of the development of hHcy conditions (direct Hcy subcutaneous administration or by Met-enriched diet) could lead to the different levels of histological damage, probably influenced by Hcy itself or its toxic metabolites.…”

Molecular and Cellular Complexity of Glioma. Focus on Tumour Microenvironment and the Use of Molecular and Imaging Biomarkers to Overcome Treatment Resistance

“…Authors also found an abundance of CD11b+ GAMs inside and around the tumour [248]. We have recently developed and characterised a new TSPO radiotracer, [ 18 F]VC701 in neuroinflammation models [249]. Similarly, in an orthotopic glioma model obtained with murine GBM cells, the GL261 ones, we observed an earlier TSPO uptake signal compared to [ 18 F]FLT uptake (Figure 2).…”

PET and MRI as Yardstick for Neuro-Inflammation, a Pathological Trademark of Multiple Sclerosis (MS)

“…TSPO ligands have been inuredin experimental autoimmune encephalomyelitis (EAE), a well-accepted animal model for MS is effective in highlighting neuropathological features of MS, inclusive ofmicroglial activation [18]. 18F-VC701-PET helps to detect and follow microglia activation evolution .when18F-VC701-PET copulate with prevalent T1-gadolinium-enhanced and T2 MRI imaging theEAE-related impairments can be identified [19].…”