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

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

  • J Transl Med. 2017 Jun 19;15(1):144. doi: 10.1186/s12967-017-1245-1.
Maria Grönman 1,  Miikka Tarkia 1,  Tuomas Kiviniemi 2,  Paavo Halonen 3,  Antti Kuivanen 3,  Timo Savunen 2 4,  Tuula Tolvanen 5 6,  Jarmo Teuho 5 6,  Meeri Käkelä 1,  Olli Metsälä 1,  Mikko Pietilä 2,  Pekka Saukko 7,  Seppo Ylä-Herttuala 3,  Juhani Knuuti 1 5,  Anne Roivainen 1 5 8,  Antti Saraste 9 10 11 12
Affiliations

Affiliations

  • 1 Turku PET Centre, University of Turku, 20521, Turku, Finland.
  • 2 Heart Center, Turku University Hospital, Turku, Finland.
  • 3 A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Joensuu, Finland.
  • 4 Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
  • 5 Turku PET Centre, Turku University Hospital, Turku, Finland.
  • 6 Department of Medical Physics, Turku University Hospital and University of Turku, Turku, Finland.
  • 7 Department of Forensic Medicine, University of Turku, Turku, Finland.
  • 8 Turku Center for Disease Modeling, University of Turku, Turku, Finland.
  • 9 Turku PET Centre, University of Turku, 20521, Turku, Finland. antsaras@utu.fi.
  • 10 Heart Center, Turku University Hospital, Turku, Finland. antsaras@utu.fi.
  • 11 Turku PET Centre, Turku University Hospital, Turku, Finland. antsaras@utu.fi.
  • 12 Institute of Clinical Medicine, University of Turku, Turku, Finland. antsaras@utu.fi.
PMID: 28629432 DOI: 10.1186/s12967-017-1245-1
Abstract

Background: 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 [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.

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 [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.

Results: Stent 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.

Conclusions: Cardiac [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.

Keywords

Angiogenesis; Myocardial ischemia; Positron emission tomography; αvβ3 integrin.

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