Angiogenesis PET Tracer Uptake (68Ga-NODAGA-E[(cRGDyK)]2) in Induced Myocardial Infarction and Stromal Cell Treatment in Minipigs
Thomas Rasmussen,
Bjarke Follin,
Jens Kastrup,
Malene Brandt-Larsen,
Jacob Madsen,
Thomas Emil Christensen,
Morten Juhl,
Smadar Cohen,
Karsten Pharao Hammelev,
Christian Holdflod Møller,
Jens Peter Goetze,
Philip Hasbak,
Andreas Kjær
Affiliations
Thomas Rasmussen
Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark
Bjarke Follin
Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark
Jens Kastrup
Cardiology Stem Cell Centre, Department of Cardiology, The Heart Centre, Rigshospitalet, University of Copenhagen, 1165 Copenhagen, Denmark
Malene Brandt-Larsen
Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark
Jacob Madsen
Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark
Thomas Emil Christensen
Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark
Morten Juhl
Cardiology Stem Cell Centre, Department of Cardiology, The Heart Centre, Rigshospitalet, University of Copenhagen, 1165 Copenhagen, Denmark
Smadar Cohen
Avram and Stella Goldstein-Goren Department of Biotechnology Engineering and Regenerative Medicine and Stem Cell (RMSC) Research Center, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
Karsten Pharao Hammelev
Department of Experimental Medicine, University of Copenhagen, 1165 Copenhagen, Denmark
Christian Holdflod Møller
Department of Cardiothoracic Surgery, The Heart Centre, Rigshospitalet, University of Copenhagen, 1165 Copenhagen, Denmark
Jens Peter Goetze
Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen, Denmark
Philip Hasbak
Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark
Andreas Kjær
Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark
Angiogenesis is considered integral to the reparative process after ischemic injury. The αvβ3 integrin is a critical modulator of angiogenesis and highly expressed in activated endothelial cells. 68Ga-NODAGA-E[(cRGDyK)]2 (RGD) is a positron-emission-tomography (PET) ligand targeted towards αvβ3 integrin. The aim was to present data for the uptake of RGD and correlate it with histology and to further illustrate the differences in angiogenesis due to porcine adipose-derived mesenchymal stromal cell (pASC) or saline treatment in minipigs after induction of myocardial infarction (MI). Three minipigs were treated with direct intra-myocardial injection of pASCs and two minipigs with saline. MI was confirmed by 82Rubidium (82Rb) dipyridamole stress PET. Mean Standardized Uptake Values (SUVmean) of RGD were higher in the infarct compared to non-infarct area one week and one month after MI in both pASC-treated (SUVmean: 1.23 vs. 0.88 and 1.02 vs. 0.86, p < 0.05 for both) and non-pASC-treated minipigs (SUVmean: 1.44 vs. 1.07 and 1.26 vs. 1.04, p < 0.05 for both). However, there was no difference in RGD uptake, ejection fractions, coronary flow reserves or capillary density in histology between the two groups. In summary, indications of angiogenesis were present in the infarcted myocardium. However, no differences between pASC-treated and non-pASC-treated minipigs could be demonstrated.
