Abstract
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Objectives Multiple Sclerosis (MS) has been extensively studied as an inflammatory demyelinating condition in the central nervous system (CNS). For staple functional recovery in patients with MS, novel therapeutic interventions aiming at myelin repair are needed. Thus we developed a new PET probe ([11C]MeDAS) that can readily penetrate the blood brain barrier and selectively bind to myelin membranes. Here we report in vivo [11C]MeDAS-PET characterization of myelination in the spinal cord in an experimental autoimmune encephalomyelitis (EAE) rat model.
Methods 1) EAE was induced in Lewis rat using a recombinant myelin oligodendrocyte glycoprotein (MOG), yielding acute clinical disease that reflects extensive spinal cord demyelination and inflammation. 2) Longitudinal microPET/CT studies were performed at different disease stages following i.v. injection of [11C]MeDAS in comparison with baseline scan. For quantitative analysis, spines were defined as volume of interest based on CT images and used to measure the radioactivity concentration. 3) Ex vivo MeDAS staining was performed after imaging studies. 4) To differentiate the effect of demyelination from inflammation on [11C]MeDAS uptake, microPET studies were conducted in an acute neuroinflammation rat model without myelin damage in the brain. All microPET studies were correlated with immunohistology studies.
Results 1) Ex vivo tissue staining showed decreased MeDAS staining in EAE spinal cord compared with the control. 2) Quantitative microPET analysis of [11C]MeDAS in rat EAE models demonstrated the uptake of [11C]MeDAS in spinal cord (T6-L3) were significantly decreased following disease onset. 3) Quantitative microPET data and immunohistology studies showed that inflammation did not alter the pharmacokinetics of [11C]MeDAS in the CNS.
Conclusions [11C]MeDAS is a specific PET imaging marker of myelination and can be used to facilitate efficacy evaluation of myelin repair therapies currently developed.