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(Circulation. 2008;117:781-789.)
© 2008 American Heart Association, Inc.

Imaging

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

Francois Rouzet, MD; Miguel Dominguez Hernandez, MD; Florence Hervatin, PhD; Laure Sarda-Mantel, MD, PhD; Agnes Lefort, MD, PhD; Xavier Duval, MD, PhD; Liliane Louedec; Bruno Fantin, MD, PhD; Dominique Le Guludec, MD, PhD; Jean-Baptiste Michel, MD, PhD

From AP-HP, Groupe Hospitalier Bichat-Claude Bernard, Service de Médecine Nucléaire; Université Denis Diderot–Paris 7, UMR S773; and INSERM U773, Paris, France (F.R., L.S.-M., D.L.G.); INSERM U698, Cardiovascular Remodeling, Paris 7 University, CHU Xavier Bichat, Paris, France (M.D.H., L.L., J.B.M.); CEA-DRM-SHFJ, Orsay, France (F.H.); EA3964, Université Denis Diderot–Paris 7, Paris, France (A.L., B.F); INSERM CIC 007; AP-HP, Groupe Hospitalier Bichat-Claude Bernard, Centre d’Investigation Clinique; Université Denis Diderot–Paris 7, Paris, France (X.D.); and Department of Pathology, University of Guadalajara, Guadalajara, Mexico (M.D.H.).

Correspondence to François Rouzet, MD, Service de Médecine Nucléaire, Hôpital Bichat, 46 rue Henri-Huchard, 75018 Paris, France. E-mail francois.rouzet{at}bch.aphp.fr

Received June 1, 2007; accepted November 29, 2007.

Background— 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.

Methods and Results— 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.

Conclusions— ^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.

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CLINICAL PERSPECTIVE

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Clinical Summaries
Circulation 2008 117: 711-713. [Full Text]