This Article Full Text Full Text (PDF) All Versions of this Article: 117/6/781    most recent CIRCULATIONAHA.107.718114v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Rouzet, F. Articles by Michel, J.-B. PubMed PubMed Citation Articles by Rouzet, F. Articles by Michel, J.-B. Related Collections Coagulation and fibronolysis Aggregation Platelets Cardiovascular imaging agents/Techniques Other Vascular biology Nuclear cardiology and PET Animal models of human disease Related Article

(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.

---

 

CLINICAL PERSPECTIVE

Related Article:

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