Noninvasive imaging of myocardial angiogenesis following experimental myocardial infarction

Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8017, USA.
Journal of Clinical Investigation (Impact Factor: 13.77). 07/2004; 113(12):1684-91. DOI: 10.1172/JCI20352
Source: PubMed

ABSTRACT Noninvasive imaging strategies will be critical for defining the temporal characteristics of angiogenesis and assessing efficacy of angiogenic therapies. The alphavbeta3 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 ((111)In-labeled) alphavbeta3-targeted agent in the region of injury-induced angiogenesis in a chronic rat model of infarction. The specificity of the targeted alphavbeta3-imaging agent for angiogenesis was established using a nonspecific control agent. The potential of this radiolabeled alphavbeta3-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 (111)In-labeled alphavbeta3-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 alphavbeta3 integrin. Thus, angiogenesis in the heart can be imaged noninvasively with an (111)In-labeled alphavbeta3-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.

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Available from: Joseph A Madri, Aug 22, 2015
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    • "More recently, a number of investigators have demonstrated the feasibility of noninvasive evaluation of angiogenesis using imagebased approaches targeted at cell surface receptors. We previously demonstrated the potential of single photon emission computed tomographic (SPECT) imaging with radiolabeled tracers targeted at α v integrins and X-ray computed tomography (CT) for evaluation of spatial and temporal changes in peripheral [19] and in myocardial angiogenesis in mice [20], rats, and dogs post-MI [21] [22]. "
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    ABSTRACT: Insulin-like growth factor-1 (IGF-1) has been found to exert favorable effects on angiogenesis in prior animal studies. This study explored the long-term effect of IGF-1 on angiogenesis using microSPECT-CT in infarcted rat hearts after delivering human IGF-1 gene by adeno-associated virus (AAV). Myocardial infarction (MI) was induced in Sprague-Dawley rats by ligation of the proximal anterior coronary artery and a total of 1011 AAV-CMV-lacZ (control) or IGF-1 vectors were injected around the peri-infarct area. IGF-1 expression by AAV stably transduced heart muscle for up to 16 weeks post-MI and immunohistochemistry revealed a remarkable increase in capillary density. A 99mTc-labeled RGD peptide (NC100692, GE Healthcare) was used to assess temporal and regional αv integrin activation. Rats were injected with NC100692 followed by 201Tl chloride and in vivo microSPECT-CT imaging was performed. After imaging, hearts were excised and cut for quantitative gamma-well counting (GWC). NC100692 retention was significantly increased in hypoperfused regions of both lacZ and IGF-1 rats at 4 and 16 weeks post-MI. Significantly higher activation of αv integrin was observed in IGF-1 rats at 4 weeks after treatment compared with control group, although the activation was lower in the IGF-1 group at 16 weeks. Local IGF-1 gene delivery by AAV can render a sustained transduction and improve cardiac function post-MI. IGF-1 expression contributes to enhanced αv integrin activation which is linked to angiogenesis. MicroSPECT-CT imaging with 99mTc-NC100692 and quantitative GWC successfully assessed differences in αv integrin activation between IGF-1-treated and control animals post-MI.
    Journal of Molecular and Cellular Cardiology 06/2010; 48(6-48):1071-1079. DOI:10.1016/j.yjmcc.2009.10.008 · 5.22 Impact Factor
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    ABSTRACT: Not available Biomedical Engineering
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