Changes Of Dopamine Transporter Detected By C-11-Cft Pet In Lrrk2-Knockoutand G2019 Transgenicmice

1379 Objectives: Mutation of the leucine-rich repeat kinase 2 (LRRK2) gene is most common genic factor of Parkinson’s Disease (PD). Dopamine loss in striatumis linked to the disease severity of PD, and the deduction can be detected by dopamine transporter (DAT) positron emission tomography (PET). Alternation of DAT expression in G2019S-LRRK2 and LRRK2 knockout (KO) mice is critical to investigate the pathological influence of LRRK2 mutation in DAT. To explore this influence, 11C-CFT PET were performed in LRRK2 transgenic mice by small animal PET/CT.Methods: Static small animal PET/CT imaging was obtained for 20 min at 40 min post intravenous injection of 11C-CFT in G2019-LRRK2 transgenic mice (n = 4),the LRRK2-knockout mice (n = 6) and control C57BL/6 mice (n = 6). All CFT images were spatially normalized into PET template by using Pmod 3.5; then the voxel size of all images was scaled by 10 so that the default parameters in SPM12 could be applied and the images were smooth with a gaussian kernel. Finally, two-sample t test between G2019-LRRK2, LRRK2-knockout mice and C57BL/6 mice was performed respectively by SPM12 to explore the changed DAT expression in G2019-LRRK2, LRRK2-knockout mice. The statistical significance was set at p Results: Compared with control C57BL/6 mice, 11C-CFT uptake in right medial striatum and left posterior striatum of LRRK2-KO mice was significantly increased, while 11C-CFT uptake in right anterior ventral striatum of G2019S-LRRK2 mice was significantly decreased. Furthermore, the increased clusters of LRRK2-KO compared to G2019S were right medial striatum and left anterior striatum.Conclusion: The increased uptake of 11C-CFTin LRRK2-KO mice indicates the enhancive expression of DAT while the decreased uptake in G2019S-LRRK2 transgenic mice indicates the deduction. These results bidirectionally validated the effect of LRRK2 mutation on DAT expression. Acknowledgements: This research project was supported by the National Natural Science Foundation of China (No. 81571345, 81801752,81771179 ).