Abstract
BackgroundRadiolabeled RGD peptides detect αvβ3 integrin expression associated with angiogenesis and extracellular matrix remodeling after myocardial infarction. We studied whether cardiac positron emission tomography (PET) with [68Ga]NODAGA-RGD detects increased αvβ3 integrin expression after induction of flow-limiting coronary stenosis in pigs, and whether αvβ3 integrin is expressed in viable ischemic or injured myocardium.MethodsWe 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 [68Ga]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 [15O]water PET. Guided by triphenyltetrazolium chloride staining, tissue samples from viable and injured myocardial areas were obtained for autoradiography and histology.ResultsStent implantation resulted in a partly reversible myocardial perfusion abnormality. Compared with remote myocardium, [68Ga]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 [68Ga]NODAGA-RGD uptake than the remote non-ischemic myocardium. Uptake of [68Ga]NODAGA-RGD correlated with immunohistochemical detection of αvβ3 integrin that was expressed in the injured myocardial areas.ConclusionsCardiac [68Ga]NODAGA-RGD PET demonstrates increased myocardial αvβ3 integrin expression after induction of flow-limiting coronary stenosis in pigs. Localization of [68Ga]NODAGA-RGD uptake indicates that it reflects αvβ3 integrin expression associated with repair of recent myocardial injury.
Highlights
Radiolabeled radiolabelled arginyl-glycyl-aspartic acid (RGD) peptides detect αvβ3 integrin expression associated with angiogenesis and extracel‐ lular matrix remodeling after myocardial infarction
The main findings of the present study are that [68Ga] NODAGA-RGD cardiac positron emission tomography (PET) detected increased myocardial αvβ3 integrin expression two weeks after induction of flow-limiting coronary stenosis in pig
Αvβ3 integrin expression and [68Ga]NODAGA-RGD uptake localized to the irreversibly injured myocardium, whereas tracer uptake was absent in viable ischemic areas
Summary
Radiolabeled RGD peptides detect αvβ integrin expression associated with angiogenesis and extracel‐ lular matrix remodeling after myocardial infarction. We studied whether cardiac positron emission tomography (PET) with [68Ga]NODAGA-RGD detects increased αvβ integrin expression after induction of flow-limiting coronary stenosis in pigs, and whether αvβ integrin is expressed in viable ischemic or injured myocardium. Grönman et al J Transl Med (2017) 15:144 flow-limiting coronary stenosis and whether αvβ integrin expression is induced in viable or irreversibly injured myocardium. In order to study the effects of flow-limiting coronary stenosis on myocardial expression of αvβ integrin, we performed cardiac positron emission tomography (PET) with 68Gallium-labeled 1,4,7-triazacyclononane1-glutaric acid-4,7-diacetic acid conjugated RGD peptide ([68Ga]NODAGA-RGD), a myocardial perfusion PET, and a histological evaluation of myocardial injury and αvβ integrin expression in pigs. We compared [68Ga]NODAGA-RGD uptake in the ischemic myocardium and the remote non-ischemic myocardium as well as in the viable and injured ischemic myocardial areas 2 weeks after the induction of stenosis
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