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.

Background— Time-dependent activation of matrix metalloproteinases (MMPs) after myocardial infarction (MI) contributes to adverse left ventricular (LV) remodeling; however, noninvasive methods to monitor this process serially are needed. Methods and Results— MMP-targeted radiotracers were developed that displayed selective binding kinetics to the active MMP catalytic domain. Initial nonimaging studies were performed with a ¹¹¹ In-labeled MMP-targeted radiotracer ( ¹¹¹ In-RP782) and negative control compound ( ¹¹¹ In-RP788) in control mice (Ctrl) and in mice 1 week after surgically induced MI. Localization of ¹¹¹ In-RP782 was demonstrated within the MI by microautoradiography. A 334±44% increase ( P <0.001 versus Ctrl) in relative retention of ¹¹¹ In-RP782 was confirmed by gamma well counting of myocardium. Subsequent high-resolution dual-isotope planar and hybrid micro–single-photon emission computed tomography/CT imaging studies with an analogous ^99m Tc-labeled MMP-targeted radiotracer ( ^99m Tc-RP805) and ²⁰¹ Tl demonstrated favorable biodistribution and clearance kinetics of ^99m Tc-RP805 for in vivo cardiac imaging, with robust retention 1 to 3 weeks after MI in regions of decreased ²⁰¹ Tl perfusion. Gamma well counting yielded a similar ≈300% increase in relative myocardial retention of ^99m Tc-RP805 in MI regions (Ctrl, 102±9%; 1 week, 351±77%; 2 weeks, 291±45%; 3 weeks, 292±41%; P <0.05 versus Ctrl). Myocardial uptake in the MI region was also significantly increased ≈5-fold when expressed as percentage injected dose per gram tissue. There was also a significant 2-fold increase in myocardial activity in remote regions relative to control mice, suggesting activation of MMPs in regions remote from the MI. Conclusions— This novel noninvasive targeted MMP radiotracer imaging approach holds significant diagnostic potential for in vivo localization of MMP activation and tracking of MMP-mediated post-MI remodeling.

A healthy, functional microcirculation in combination with nonobstructed epicardial coronary arteries is the prerequisite of normal myocardial perfusion. Quantitative assessment in myocardial perfusion and determination of absolute myocardial blood flow can be achieved noninvasively using dynamic imaging with multiple imaging modalities. Extensive evidence supports the clinical value of noninvasively assessing indices of coronary flow for diagnosing coronary microvascular dysfunction; in certain diseases, the degree of coronary microvascular impairment carries important prognostic relevance. Although, currently positron emission tomography is the most commonly used tool for the quantification of myocardial blood flow, other modalities, including single-photon emission computed tomography, computed tomography, magnetic resonance imaging, and myocardial contrast echocardiography, have emerged as techniques with great promise for determination of coronary microvascular dysfunction. The following review will describe basic concepts of coronary and microvascular physiology, review available modalities for dynamic imaging for quantitative assessment of coronary perfusion and myocardial blood flow, and discuss their application in distinct forms of coronary microvascular dysfunction.

In Part I of this consensus article, the imaging methodology, evolving imaging technology, and development of novel targeted molecular probes relevant to the developing field of cardiovascular molecular imaging were reviewed. Novel reporter gene and reporter probe imaging approaches for tracking of cardiac transgene expression were also discussed and have important future implications for evaluation of gene- and cell-based therapies for the failing heart. The current role of metabolic and receptor imaging was also briefly reviewed, as these represent the beginning of our clinical application of molecular imaging within the cardiovascular system. Part II will summarize the available targeted imaging probes as well as specific future applications of molecular imaging for identification and evaluation of critical pathophysiological processes of the cardiovascular system.