Serial F18-FDG PET-Guided Histological Characterization of Myocardial Infiltrating Cells in a Rat Model of Acute Myocarditis

1633 Objectives Inflammation is a highly dynamic and variable complex process involving multiple cell types. We hypothesized that non-invasive serial monitoring of inflammatory activity can provide better understanding of post-mortem histological findings. In a rat model of acute autoimmune myocarditis, we aimed to characterize the cellular expression of adhesion molecules also known as markers for vascular-resident stem and progenitor cells in association with the time course of global inflammatory activity as monitored by serial 18F-FDG PET. Methods In Lewis rats autoimmune myocarditis was induced by immunizing twice at a week (wk) interval with 10mg/ml porcine cardiac myosin with Freund9s complete adjuvant. Two wks after the initial immunization, rats underwent serial weekly 18F-FDG imaging (after overnight fasting) utilizing a dedicated small animal PET system. Rats were euthanized at wk 3 (n=4) or 5 (n=5) after the last PET imaging session for histological analysis. Standard immunohistochemical staining was served to determine of the expression of CD44 (a cell surface molecule expressed on the majority of inflammatory cells as well as on vascular-resident stem and progenitor cells, responsible for adhesion to the extracellular matrix hyaluronic acid) and CD34 (a endothelial, vascular stem and progenitor cell marker playing a role in cell adhesion and homing during inflammation) in the inflammatory lesions. Results Serial PET imaging of the myocardium revealed intense focal 18F-FDG accumulation at wk 3 followed by a rapid decline at wk 4 and 5 (18F-FDG uptake in the heart of 2nd, 3rd, 4th and 5th wk: 0.4 ± 0.2, 0.9 ± 0.2, 0.2 ± 0.1, 0.2 ± 0.1 %ID, respectively, [asterisk]P Conclusions By serial PET monitoring of myocardial inflammatory activity we could specifically follow both the temporal and spatial expression of key adhesion molecules on infiltrating cells as well as on local vascular-resident stem and progenitor cells in a rat model of acute myocarditis.