Metabolic changes in an animal model of Amyotrophic Lateral Sclerosis by [F-18]-Fluorodeoxyglucose

• Aim/Introduction: Amyotrophic Lateral Sclerosis (ALS) isa fatal neurodegenerative disorder that affects motorneurons, leading to muscle atrophy, paralysis, and eventuallyrespiratory failure. As with many other neurodegenerativedisorders, neuronal apoptosis is often associated with aloss of neuronal function and metabolic changes. [18F]-FDG is a well-validated biomarker to observe metabolicchanges in several brain disorders in humans, but its usein preclinical ALS research is not yet widespread. We aim tocompare [18F]-FDG uptake in SOD1G93A and wild-type beforethe development of terminal ALS symptoms.Materials and Methods: animals (6 SOD1WT, 7 SOD1G93A) were previouslygenotyped for mutant SOD1 using qPCR. When SOD1G93Aanimals started to develop ALS-like symptoms, animals werefasted for 4 hours and then injected intravenously with [18F]-FDG (injected dose of 10.8±2 MBq). One hour after injection,animals were placed in a microPET-CT scanner (MedisonanoPET-CT) and scanned (5 minutes for CT, 10 minutesfor PET). CT data was used for attenuation correction. Afterreconstruction, data were coregistered to an MRI templateand brain VOIs were created for several regions and dividedbetween left and right hemispheres using the Allen mousebrain atlas as a VOI template and the uptake of each ROIwas calculated to the whole-brain (SUVR) with T-test.P<0.05 was used for statistical significance.Results: OurSUVR data suggest a significant metabolic deregulationin SOD1G93A animals when analyzing [18F]-FDG in the brain.There was significant hypometabolism in anterior cingulatecortex (9% decrease in SOD1G93A vs. SOD1WT for both left and right hemispheres), in left entorhinal cortex (14%decrease), left hippocampus (12% decrease), right noseassociated primary somatosensory cortex (6% decrease),left supplementary somatosensory cortex (8% decrease),thalamus (11% and 8% for left and right, respectively),and right vermal region of the cerebellum (9% decrease).Hypermetabolism was, on the other hand, found in pallidum(12% increase in SOD1G93A vs. SOD1WT), lateral amygdala (41%and 64% increase in left and right, respectively), and corticalamygdala (98% increase for both left and right).Conclusion:These preliminary findings suggest a significant metabolicderegulation in animals with mutant SOD1 that developALS disease. Since animals were scanned after developingALS symptoms, further studies aimed to study brainmetabolism with [18F]-FDG in prodromal stages of diseaseare warranted. This would provide us better insight intothe usefulness of metabolic radiotracers for the detectionof disease onset and progression, as well as the efficacy oftherapeutic treatment strategies.References: None

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MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)

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