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
  • 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. [email protected].
  • 10. Heart Center, Turku University Hospital, Turku, Finland. [email protected].
  • 11. Turku PET Centre, Turku University Hospital, Turku, Finland. [email protected].
  • 12. Institute of Clinical Medicine, University of Turku, Turku, Finland. [email protected].
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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