Technetium 99m–Labeled Annexin V Scintigraphy of Platelet Activation in Vegetations of Experimental Endocarditis

Abstract

The pathophysiology of infective endocarditis involves a pathogen/host tissue interaction, leading to formation of infected thrombotic vegetations. Annexin V is a ligand of phosphatidylserines exposed by activated platelets and apoptotic cells. Because vegetations are platelet-fibrin clots in which platelet proaggregant activity is enhanced by bacterial colonization, we investigated the ability of annexin V labeled with technetium Tc 99m (99mTc-ANX) to provide functional imaging of these vegetations in experimental models of infective endocarditis. This ability was assessed in rabbits and rats because of the different interest of these 2 species in preclinical analysis. Nonbacterial thrombotic endocarditis was induced with the use of a catheter left indwelling through the aortic or tricuspid valve, and animals were injected with either a bacterial inoculum or saline. Scintigraphic investigations were performed 5 days later and showed a higher 99mTc-ANX uptake by vegetations in infected versus noninfected animals (ratio, 1.3 for in vivo acquisitions and 2 for autoradiography; P<0.0001 for all), whereas no significant uptake was present in controls. Right-sided endocarditis was associated with pulmonary uptake foci corresponding to emboli. Histological analysis of vegetations showed a specific uptake of 99mTc-ANX at the interface between circulating blood and vegetation. In parallel, underlying myocardial tissue showed myocyte apoptosis and mucoid degeneration, without extracellular matrix degradation at this stage. 99mTc-ANX is suitable for functional imaging of platelet-fibrin vegetations in endocarditis, as well as embolic events. 99mTc-ANX uptake reflects mainly platelet activation in the luminal layer of vegetations. This uptake is enhanced by bacterial colonization.