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Noninvasive imaging of myocardial angiogenesis following experimental myocardial infarction
David F. Meoli, … , Barry L. Zaret, Albert J. Sinusas
David F. Meoli, … , Barry L. Zaret, Albert J. Sinusas
Published June 15, 2004
Citation Information: J Clin Invest. 2004;113(12):1684-1691. https://doi.org/10.1172/JCI20352.
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Article Cardiology

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

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Figure 3

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γ-Well counting of myocardial radiotracer activity in relationship to 20...
γ-Well counting of myocardial radiotracer activity in relationship to 201Tl uptake in the chronic rat model. Data are shown for rats injected with either 111In-RP748 (RP748) or control compound. Decreased myocardial 201Tl uptake was consistently observed in the anterolateral wall, as shown in representative myocardial count profiles (A). Cntrl, control; ant, anterior; sept, septal; post, posterior; lat, lateral. Uptake of 111In-RP748 was highest in infarcted regions with reduced 201Tl retention. In contrast, myocardial uptake of the control compound tracked 201Tl perfusion. On average the relative myocardial retention of 111In-RP748 in the post-ischemic and infarcted regions was nearly twice that in regions with normal 201Tl perfusion; however, no selective retention of the nonspecific control compound was observed (B). *P < 0.05 vs. 81_120%; #P < 0.05 vs. control.

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