[18F]FDG PET/CT Studies in Parkinson’s Disease Mouse Model of α-Syncleinopathy

1613 Objectives: Aggregation of misfolded α-synuclein in intracellular inclusions, Lewy bodies (LB) are some hallmarks of human PD. To study α-synucleinopathy in vivo we have now used transgenic mice that express the A53T mutant α-synuclein protein at six times the level of endogenous mouse α-synuclein. The model is useful in assessing non-motor deficits at earlier stages of onset of PD. Here we report our findings on metabolic changes using [18F]FDG PET/CT in the Hualpha-Syn(A53T) PD mouse model. Methods: Male (n=4) and female (n=4), 6-month old hemizygous Hualpha-Syn(A53)T and no-carrier male(n=4) and female (n=4) mice from Jackson Labs were used in the study. Mice were imaged twice, at 7 months and 9 months. All mice were fasted for at least 20 hours. [18F]FDG (from PETNET solutions) was injected intraperitoneally in normal saline (approx. 7.4 MBq) under 2% isoflurane anesthesia. Mice were then awake after [18F]FDG injections and free to move in their cages. They were placed in the supine position in a mouse holder and anesthetized with 2% isoflurane for whole-body PET/CT imaging. The mouse holder was placed on the PET/CT bed and 15 minute-long PET scans were acquired 120 minutes after [18F]FDG injections. All animals had a 10-minute-long CT scan after the PET scan for attenuation correction and anatomical delineation of PET images. An Inveon Multimodality scanner was used for acquisitions in combined PET/CT experiments. Brain images were analyzed using PMOD, with PET images coregistered to a mouse brain MRI template. Regions were preidentified on the MRI template. The magnitude of [18F]FDG uptake in the brain was expressed as standard uptake value (SUV) which was computed as the average [18F]FDG activity in each volume of interest, VOI (in kBq/mL) divided by the injected dose (in MBq) times the bodyweight of each animal (in Kg). Male and female animals were analyzed as two separate groups. Results: Hualpha-Syn(A53) mice had lower [18F]FDG uptake in several brain regions compared to the no-carrier mice (Fig-1). SUV values Hualpha-Syn(A53) male: midbrain=1.82, neocortex=1.59, thalamus=1.60, hippocampus=1.53, olfactory bulb= 1.78 versus no-carrier midbrain=2.40, neocortex=2.25, thalamus=2.41, hippocampus=2.18, olfactory bulb= 2.54. SUV values Hualpha-Syn(A53) female: midbrain=2.34, neocortex=1.81, thalamus=2.00, hippocampus=1.77, olfactory bulb=1.82 versus no-carrier midbrain=2.83, neocortex=2.32, thalamus=2.46, hippocampus=2.36, olfactory bulb=2.27. The hemizygous mice develop adult-onset neurodegenerative disease between 9-16 months of age, with a progressive motoric dysfunction leading to death. We see significant reductions in [18F]FDG at 9 months of age. Male mice showed greater reductions (up to 30%) compared to the female mice (Fig-2). The transgenic mice did not show any motoric dysfunctions, however; two PD mice showed hind limb paralysis. Conclusion: Significant decreases of [18F]FDG uptake in the Hualpha-Syn(A53) PD mouse model was observed at 9 months of age. This is consistent with the cortical hypometabolism in PD patients. Thus, this may be a suitable model for studies related to PD for the discovery of new biomarkers.