Longitudinal (18)F-FDG PET imaging in a rat model of autoimmune myocarditis

AIMS: Although mortality rate is very high, diagnosis of acute myocarditis remains challenging with conventional tests. We aimed to elucidate the potential role of longitudinal 2-Deoxy-2-(18)F-fluoro-D-glucose ((18)F-FDG) positron emission tomography (PET) inflammation monitoring in a rat model of experimental autoimmune myocarditis. METHODS AND RESULTS: Autoimmune myocarditis was induced in Lewis rats by immunizing with porcine cardiac myosin emulsified in complete Freund’s adjuvant. Time course of disease was assessed by longitudinal (18)F-FDG PET imaging. A correlative analysis between in- and ex vivo(18)F-FDG signalling and macrophage infiltration using CD68 staining was conducted. Finally, immunohistochemistry analysis of the cell-adhesion markers CD34 and CD44 was performed at different disease stages determined by longitudinal (18)F-FDG PET imaging. After immunization, myocarditis rats revealed a temporal increase in (18)F-FDG uptake (peaked at week 3), which was followed by a rapid decline thereafter. Localization of CD68 positive cells was well correlated with in vivo(18)F-FDG PET signalling (R(2) = 0.92) as well as with ex vivo(18)F-FDG autoradiography (R(2) = 0.9, P < 0.001, respectively). CD44 positivity was primarily observed at tissue samples obtained at acute phase (i.e. at peak (18)F-FDG uptake), while CD34-positive staining areas were predominantly identified in samples harvested at both sub-acute and chronic phases (i.e. at (18)F-FDG decrease). CONCLUSION: (18)F-FDG PET imaging can provide non-invasive serial monitoring of cardiac inflammation in a rat model of acute myocarditis.