Angiogenesis PET Tracer Uptake (68Ga-NODAGA-E[(cRGDyK)]2) in Induced Myocardial Infarction and Stromal Cell Treatment in Minipigs

• Main Authors: 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
• Format: Article
• Language: English
• Published: MDPI AG 2018-05-01
• Series: Diagnostics
• Subjects: myocardial perfusion; RGD; rubidium; cardiac positron-emission-tomography; angiogenesis; mesenchymal stromal cells; hydrogel; stem cell; myocardial infarction
• Online Access: http://www.mdpi.com/2075-4418/8/2/33

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.