Noninvasive imaging of myocardial angiogenesis following experimental myocardial infarction

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Abstract

Noninvasive imaging strategies will be critical for defining the temporal characteristics of angiogenesis and assessing efficacy of angiogenic therapies. The αvβ3 integrin is expressed in angiogenic vessels and represents a potential novel target for imaging myocardial angiogenesis. We demonstrated the localization of an indium-111–labeled (111In-labeled) αvβ3-targeted agent in the region of injury-induced angiogenesis in a chronic rat model of infarction. The specificity of the targeted αvβ3-imaging agent for angiogenesis was established using a nonspecific control agent. The potential of this radiolabeled αvβ3-targeted agent for in vivo imaging was then confirmed in a canine model of postinfarction angiogenesis. Serial in vivo dual-isotope single-photon emission–computed tomographic (SPECT) imaging with the 111In-labeled αvβ3-targeted agent demonstrated focal radiotracer uptake in hypoperfused regions where angiogenesis was stimulated. There was a fourfold increase in myocardial radiotracer uptake in the infarct region associated with histological evidence of angiogenesis and increased expression of the αvβ3 integrin. Thus, angiogenesis in the heart can be imaged noninvasively with an 111In-labeled αvβ3-targeted agent. The noninvasive evaluation of angiogenesis may have important implications for risk stratification of patients following myocardial infarction. This approach may also have significant clinical utility for noninvasively tracking therapeutic myocardial angiogenesis.

Authors

David F. Meoli, Mehran M. Sadeghi, Svetlana Krassilnikova, Brian N. Bourke, Frank J. Giordano, Donald P. Dione, Haili Su, D. Scott Edwards, Shuang Liu, Thomas D. Harris, Joseph A. Madri, Barry L. Zaret, Albert J. Sinusas