Imaging of α(v)β(3) integrin expression in experimental myocardial ischemia with [(68)Ga]NODAGA-RGD positron emission tomography

BACKGROUND: 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. 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 [(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. RESULTS: 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. CONCLUSIONS: 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.