PET imaging of demyelination and remyelination in the cuprizone mouse model for multiple sclerosis:A comparison between [C-11]CIC and [C-11]MeDAS

Multiple Sclerosis (MS) is a neurodegenerative disease characterized by demyelinated lesions. PET imaging using specific myelin radioligands might solve the lack of a specific imaging tool for diagnosing and monitoring demyelination and remyelination in MS patients. In recent years, a few tracers have been developed for in vivo PET imaging of myelin, but they have not been fully evaluated yet. In this study, we compared [(11)C]CIC and [(11)C]MeDAS as PET tracers for monitoring demyelination and remyelination in cuprizone-fed mice. The ex vivo biodistribution of [(11)C]CIC showed decreased tracer uptake in mice fed with 0.2% cuprizone diet for 5 weeks, as compared to control mice. However, tracer uptake did not increase again after normal diet was restored for 5 weeks (remyelination). Surprisingly, in vivo PET imaging with [(11)C]CIC in cuprizone-fed mice revealed a significant reduction in whole brain tracer uptake after 5 weeks of remyelination. No correlation between ex vivo biodistribution and in vivo imaging data was found for [(11)C]CIC (r(2)=0.15, p=0.11). However, a strong correlation was found for [(11)C]MeDAS (r(2)=0.88, p<0.0001). [(11)C]MeDAS ex vivo biodistribution revealed significant decreased brain uptake in the demyelination group, as compared to controls and increased the tracer uptake after 5 weeks of remyelination. [(11)C]MeDAS images showed a low background signal and clear uptake in the brain white matter and spinal cord. Taken together, the results of this comparative study between [(11)C]CIC and [(11)C]MeDAS clearly show that [(11)C]MeDAS is the preferred PET tracer to monitor myelin changes in the brain and spinal cord in vivo.