Title |
Imaging of αvβ3 integrin expression in experimental myocardial ischemia with [68Ga]NODAGA-RGD positron emission tomography
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Published in |
Journal of Translational Medicine, June 2017
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DOI | 10.1186/s12967-017-1245-1 |
Pubmed ID | |
Authors |
Maria Grönman, Miikka Tarkia, Tuomas Kiviniemi, Paavo Halonen, Antti Kuivanen, Timo Savunen, Tuula Tolvanen, Jarmo Teuho, Meeri Käkelä, Olli Metsälä, Mikko Pietilä, Pekka Saukko, Seppo Ylä-Herttuala, Juhani Knuuti, Anne Roivainen, Antti Saraste |
Abstract |
Radiolabeled 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 [(68)Ga]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. 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 αvβ3 integrin that was expressed in the injured myocardial areas. Cardiac [(68)Ga]NODAGA-RGD PET demonstrates increased myocardial αvβ3 integrin expression after induction of flow-limiting coronary stenosis in pigs. Localization of [(68)Ga]NODAGA-RGD uptake indicates that it reflects αvβ3 integrin expression associated with repair of recent myocardial injury. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 3 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 67% |
Scientists | 1 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 43 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 8 | 19% |
Student > Doctoral Student | 6 | 14% |
Researcher | 4 | 9% |
Professor | 4 | 9% |
Student > Bachelor | 2 | 5% |
Other | 9 | 21% |
Unknown | 10 | 23% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 13 | 30% |
Biochemistry, Genetics and Molecular Biology | 6 | 14% |
Psychology | 3 | 7% |
Agricultural and Biological Sciences | 2 | 5% |
Neuroscience | 2 | 5% |
Other | 5 | 12% |
Unknown | 12 | 28% |