Mapping alteration of dopaminergic neurons in a rat model of Parkinson Disease through the comparison of the presynaptic PET tracers

ABSTRACT - NECTAR 2018 Parkinson’s Disease (PD) is characterized by dopaminergic neuronal loss in the substantia nigra (SN) resulting in a dopamine deficiency in the striatum.1 We developed a pathologically relevant rat model of PD using viral vectors to overexpress mutant alpha-synuclein.2 Our aims were to evaluate the dopaminergic changes and neuronal loss at different time-points in this model with two different presynaptic PET tracers, and relate imaging results with behavioural and histological changes. Therefor rats were unilaterally injected in the SN with AAV2/6 viral vector coding for mutated (A53T) human alpha-synuclein, and were studied at 6 or 12 weeks post-injection (wpi). PET imaging was performed using 6-[18F]fluoro-L-m-tyrosine3 (FMT), a substrate for AADC and [18F]-LBT9994 (LBT), a radioligand for dopamine transporter (DAT). Quantitative uptake images were calculated using Logan and Patlak graphical methods, with a cerebellar reference. At 6wpi we did not observe any asymmetry in the striatum; neither with FMT (n=5;p=0.421) nor LBT (n=6;p=0.310). At 12wpi we observed an asymmetry with LBT (n=4;p=0.003), but not with FMT (n=2;p=0.336). Histological evaluation showed 28% loss of TH-positive cells in the SN at 12wpi (n=8;p=0.031), but not at 6wpi (n=6;ns). A motor deficit was observed with the cylinder test at both time-points (n=7/8;p