For the imaging of apoptosis, recombinant human annexin A5 has been radiolabeled with 99mTc, and the feasibility

of imaging apoptosis has been demonstrated both in experimental and clinical cardiovascular disease states.17-19) Bennink et al.20) recently showed that acute doxorubicin induced cardiomyopathy based on early apoptosis can be OSI-906 imaged with 99mTc-annexin A5 scintigraphy in the murine model. In this study, we used microbubbles conjugated with annexin A5 for targeted ultrasound imaging of apoptosis. In comparison to radionuclide imaging, the high temporal resolution, availability, rapid execution of imaging protocols, and relatively low cost are features Inhibitors,research,lifescience,medical of targeted molecular imaging with ultrasound that make this technique attractive.12) As microbubbles

are pure intravascular tracers, molecular imaging with contrast-enhanced ultrasound has focused on diseases such as inflammation, thrombus formation, and angiogenesis, Inhibitors,research,lifescience,medical which are mediated by pathophysiologic events that occur within the vasculature.14) Inhibitors,research,lifescience,medical In doxorubicin-induced cardiotoxicity, both cardiomyocyte and endothelial cell death can occur via apoptosis.21) Therefore, in this study, retained microbubbles that produced contrast enhancements were thought to be adhered to the apoptotic endothelium, not to the apoptotic cardiomyocyte. However, we could not entirely exclude the possibility of direct attachment of A5MB to apoptotic cardiomyocytes by extravasation through

the disrupted microvessel. In this study, the direct visualization of A5MB binding to apoptotic cell could not be performed in in vitro tests nor in in vivo experiments. The results of this study indicate that site-targeted ultrasound has the potential for non-invasive Inhibitors,research,lifescience,medical investigation of early apoptosis preceding deterioration of LV systolic function in doxorubicin induced cardiomyopathy. However, a destructive imaging protocol that includes Inhibitors,research,lifescience,medical a 15-minute delay for wash-out may be difficult to apply clinically in the future, because precisely locating the heart before the first destructive pulse may be challenging. In addition, either contrast opacification was assessed by visual estimation rather than by a quantitative method in this study, and a newer quantification method may improve the reproducibility and practicability of targeted ultrasound imaging. In conclusion, acute doxorubicin-induced cardiomyopathy based on early apoptosis can be assessed and imaged with targeted ultrasound imaging using microbubbles conjugated with annexin A5 in rats. This investigation model may lead to interesting applications during in vivo evaluations of cardiomyocyte apoptosis in cardiomyopathy. Acknowledgements This work was supported by grants from the Korean Society of Echocardiography (Industrial-Educational Cooperation, 2005).
REFER TO THE PAGE 77-83 The study by Kim et al.