Technetium 99m-labeled annexin V scintigraphy of platelet activation in vegetations of experimental endocarditis.
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.


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.
Rouzet
Francois
F
AP-HP, Groupe Hospitalier Bichat-Claude Bernard, Service de Médecine Nucléaire, Paris, France. francois.rouzet@bch.aphp.fr
Dominguez Hernandez
Miguel
M
Hervatin
Florence
F
Sarda-Mantel
Laure
L
Lefort
Agnes
A
Duval
Xavier
X
Louedec
Liliane
L
Fantin
Bruno
B
Le Guludec
Dominique
D
Michel
Jean-Baptiste
JB
D000818:Animals; D017304:Annexin A5; D001021:Aortic Valve / Q000000981:diagnostic imaging / Q000473:pathology; D001345:Autoradiography; D004195:Disease Models, Animal; D004697:Endocarditis, Bacterial / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D013293:Enterococcus faecalis; D016908:Gram-Positive Bacterial Infections / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D015539:Platelet Activation; D011817:Rabbits; D011877:Radionuclide Imaging / Q000379:methods; D051381:Rats; D013203:Staphylococcal Infections; D013667:Technetium
D017304:Annexin A5; D013667:Technetium