Abstract
1704
Objectives Myocarditis, an inflammatory disease of the myocardium, is a major cause of death and dilated cardiomyopathy. However its work-up is not standardized due to the lack of reliable marker of progression. The disease is characterized by clusters of lymphoid and myeloid cell infiltrates, and endothelial activation which hallmark is the expression of adhesion molecules such as selectins. The aim of the study was to evaluate the ability of 99mTc-fucoidan, an imaging agent specific of selectins, in the assessment of inflammation in a model of experimental autoimmune myocarditis (EAM).
Methods EAM has been induced in male Lewis rats with purified rat cardiomyosin and compared with controls. The experiments were performed in the very early phase of myocarditis (10, 15 and 21 days after immunization) and included (1) quantification of 99mTc-fucoidan myocardial/lung ratio using SPECT/CT; (2) qualitatively: comparative analysis on adjacent slices of tracer uptake on autoradiography and selectins on immuno-histochemistry (CD62p, CD62e); and (3) quantitatively: relationship between 99mTc-fucoidan uptake by well counting (expressed as %ID/g of myocardium) and myocardial content of inflammatory cells (CD45; CD11b) using flow cytometry.
Results myocardial uptake of 99mTc-fucoidan was significantly increased in EAM compared to controls (SPECT uptake ratio: 1.6±0.1 vs. 1.2±0.4, p=0.04 at D10; 2.3±0.2 vs. 1.3±0.8, p<0.0001 at D15 and 1.9±0.2 vs. 1.3±0.3; p=0.015 at D21). Areas of 99mTc-fucoidan uptake co-localized with endothelial expression of P- and E-selectins. There was a close relationship between myocardial uptake of the tracer and content in CD45+/CD11b+ cells.
Conclusions 99mTc-fucoidan allows detecting early steps of endothelial activation associated with EAM, and its uptake is correlated with myocardial content in inflammatory cells. Further study is required to determine whether it may allow monitoring chronic disease and/or therapy efficacy.
Research Support T. Cognet was supported by a research grant from the French Federation of Cardiology