Metabolic changes in an animal model of amyotrophic lateral sclerosis evaluated by [ 18 F]-FDG positron emission tomography

Abstract Background: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized by a progressive loss of motor function and eventual death. Genetic background account for 10% of all ALS cases and several genes are associated with the onset and progression of disease in humans. Studies in humans have observed differences in glucose uptake in the brain using [ 18 F]-fluorodeoxyglucose ([ 18 F]-FDG), however, no studies in animal models of ALS have been performed on the matter. The goal of this study was to evaluate ALS-related metabolic changes in [ 18 F]-FDG uptake within the brain of transgenic mice that express a mutated human SOD1 gene (hSOD1 G93A ). Methods: Animals were genotyped for the hSOD1 G93A mutation using PCR and divided into groups according to the presence (ALS) or absence (WT) of transgene. When transgenic ALS mice started to develop motor impairment, animals were scanned for 10 minutes using PET [ 18 F]-FDG. Gender-matched WT animals were scanned at similar ages as ALS animals. The images were coregistered to an [ 18 F]-FDG template and both the standardized uptake value (SUV) and the ratio of radioactivity of target regions to the mean radioactivity of the whole brain (TRR) were calculated for 19 volumes of interest. Results: Significant effects of genotype were observed in the overall metabolic activity assessed by both SUV and ratio-to-whole brain, in which ALS mice presented with lower metabolic activity in several regions when compared with age- and gender-matched WT mice. These changes were more pronounced in hippocampus, thalamus, and midbrain. A significant effect of gender was found in the SUV of several of the regions evaluated, although these gender-related differences were not observed after normalization to the whole-brain uptake. Conclusions: The differences in [ 18 F]-FDG uptake in the brain of ALS SOD1 animals suggest a significant metabolic impairment in several of the regions evaluated. Such differences might be due to a general hypometabolic state of the animals when compared to their WT littermates. These findings suggest a possible influence of disease in brain glucose uptake and open new possibilities for the understanding of the ALS pathophysiology using animal models, as well as a possible prognostic usage of [ 18 F]-FDG in ALS in humans.