Noninvasive imaging of myocardial angiogenesis following experimental myocardial infarction

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.

cNGR: A Novel Homing Sequence for CD13/APN Targeted Molecular Imaging of Murine Cardiac Angiogenesis In Vivo

“…Several studies in different angiogenic vascular beds have been performed using an RGD conjugated contrast agent. Both radiolabeled RGD in a canine MI model 19 and magnetic resonance-focused paramagnetic-tagged RGD in a mouse tumor model 20 have been used to image neovascularization noninvasively in vivo.…”

Endothelial α ν β 3 Integrin–Targeted Fumagillin Nanoparticles Inhibit Angiogenesis in Atherosclerosis

“…11 In general, the emulsions comprised 20% (vol/vol) perfluorooctylbromide (PFO) (Minnesota Manufacturing and Mining), 2% (wt/vol) of a surfactant comixture, 1.7% (wt/vol) glycerin, and water for the balance. The surfactant comixture included 68 mole% lecithin (Avanti Polar Lipids Inc), 0.1 mole% peptidomimetic vitronectin antagonist (US Patent 6,322,770) [17][18][19] conjugated to polyethylene glycol (PEG) 2000 phosphatidylethanolamine (Avanti Polar Lipids Inc), 1.8 mole% phosphatidylethanolamine (Avanti Polar Lipids Inc), and 30 mole% gadolinium diethylene-triamine-pentaacetic acid-bis-oleate (Gateway Chemical Technologies) in chloroform:methanol (3:1), which was dried to a lipid film under vacuum. Therapeutic nanoparticle formulations included 0.2 mole% fumagillin (a gift from the National Cancer Institute), which was added to the surfactant mixture at the proportionate expense of lecithin.…”

Near-Infrared Fluorescent RGD Peptides for Optical Imaging of Integrin αvβ3 Expression in Living Mice

“…The ability to noninvasively image the integrin α v β 3 expression in living subjects would render a novel approach to diagnose tumor and its metastasis and to help to better understand tumor biology of angiogenesis, as well as to greatly facilitate the development of integrin targeted therapy. For this purpose, numerous molecular probes have been developed for imaging integrin expression using different modalities such as magnetic resonance imaging (24), ultrasound (25)(26)(27), optical imaging (28)(29)(30), positron emission tomography (PET) (31)(32)(33)(34)(35)(36)(37)(38)(39)(40), and single-photon emission computed tomography (SPECT) (41)(42)(43)(44).…”