JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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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 αv β3 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 αv β3 integrin expression after induction of flow-limiting coronary stenosis in pigs, and whether αv β3 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 αv β3 integrin that was expressed in the injured myocardial areas.

CONCLUSIONS: Cardiac [68 Ga]NODAGA-RGD PET demonstrates increased myocardial αv β3 integrin expression after induction of flow-limiting coronary stenosis in pigs. Localization of [68 Ga]NODAGA-RGD uptake indicates that it reflects αv β3 integrin expression associated with repair of recent myocardial injury.

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