Imaging of αvβ3 integrin expression in experimental myocardial ischemia with [68Ga]NODAGA-RGD positron emission tomography

Radiolabeled RGD peptides detect α v β 3 integrin expression associated with angiogenesis and extracellular matrix remodeling after myocardial infarction. We studied whether cardiac positron emission tomography (PET) with [ 68 Ga]NODAGA-RGD detects increased α v β 3 integrin expression after induction of flow-limiting coronary stenosis in pigs, and whether α v β 3 integrin is expressed in viable ischemic or injured myocardium. 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 [ 68 Ga]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 [ 15 O]water PET. Guided by triphenyltetrazolium chloride staining, tissue samples from viable and injured myocardial areas were obtained for autoradiography and histology. Stent implantation resulted in a partly reversible myocardial perfusion abnormality. Compared with remote myocardium, [ 68 Ga]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 [ 68 Ga]NODAGA-RGD uptake than the remote non-ischemic myocardium. Uptake of [ 68 Ga]NODAGA-RGD correlated with immunohistochemical detection of α v β 3 integrin that was expressed in the injured myocardial areas. Cardiac [ 68 Ga]NODAGA-RGD PET demonstrates increased myocardial α v β 3 integrin expression after induction of flow-limiting coronary stenosis in pigs. Localization of [ 68 Ga]NODAGA-RGD uptake indicates that it reflects α v β 3 integrin expression associated with repair of recent myocardial injury.