Imaging Of Alpha(V)Beta(3) Integrin Expression In Experimental Myocardial Ischemia With [Ga-68] Nodaga-Rgd Positron Emission Tomography

Background: Radiolabeled RGD peptides detect alpha(v)beta(3) integrin expression associated with angiogenesis and extracellular matrix remodeling after myocardial infarction. We studied whether cardiac positron emission tomography (PET) with [Ga-68] NODAGA-RGD detects increased alpha(v)beta(3) integrin expression after induction of flow-limiting coronary stenosis in pigs, and whether alpha(v)beta(3) integrin is expressed in viable ischemic or injured myocardium.Methods: We studied 8 Finnish landrace pigs 13 +/- 4 days after percutaneous implantation of a bottleneck stent in the proximal left anterior descending coronary artery. Antithrombotic therapy was used to prevent stent occlusion. Myocardial uptake of [Ga-68] NODAGA-RGD (290 +/- 31 MBq) was evaluated by a 62 min dynamic PET scan. The ischemic area was defined as the regional perfusion abnormality during adenosine-induced stress by [O-15] water PET. Guided by triphenyltetrazolium chloride staining, tissue samples from viable and injured myocardial areas were obtained for autoradiography and histology.Results: Stent implantation resulted in a partly reversible myocardial perfusion abnormality. Compared with remote myocardium, [Ga-68] NODAGA-RGD PET showed increased tracer uptake in the ischemic area (ischemic-to-remote ratio 1.3 +/- 0.20, p = 0.0034). Tissue samples from the injured areas, but not from the viable ischemic areas, showed higher [Ga-68] NODAGA-RGD uptake than the remote non-ischemic myocardium. Uptake of [Ga-68] NODAGA-RGD correlated with immunohistochemical detection of alpha(v)beta(3) integrin that was expressed in the injured myocardial areas.Conclusions: Cardiac [Ga-68] NODAGA-RGD PET demonstrates increased myocardial alpha(v)beta(3) integrin expression after induction of flow-limiting coronary stenosis in pigs. Localization of [Ga-68] NODAGA-RGD uptake indicates that it reflects alpha(v)beta(3) integrin expression associated with repair of recent myocardial injury.