[68Ga]Ga-NODAGA-E[(cRGDyK)]2 angiogenesis PET following myocardial infarction in an experimental rat model predicts cardiac functional parameters and development of heart failure

Figures

• 

  Figure 1. Workflow of the study. At first, the rats underwent either sham or permanent LAD-occlusion. The rats were PET/CT scanned after 1 week and follow-up scanned 4 weeks after operation. LAD, left anterior descending coronary artery; [68Ga]Ga-RGD, [68Ga]Ga-NODAGA-E[(cRGDyK)]2; PET, positron emission tomography; CT, computed tomography

• 

  Figure 2. Sensorgrams of the interaction between [68Ga]Ga-RGD and integrin αvβ3 in the present of Mg2+ (A) and Mg2+ and Mn2+ (B). The measured response is shown as the red curve, while the fitted model is the black. RU, response unit

• 

  Figure 3. Representative PET/CT images of the same rat one and four weeks after surgery. The 2-[18F]FDG -PET shows a significant lack of tracer uptake in the anterolateral parts of the myocardium at one week and four weeks post-surgery. The [68Ga]Ga-RGD PET shows that the uptake corresponds to the area with a lack of tracer uptake on the 2-[18F]FDG-PET. SA, short axis view; VLA, vertical axis view; HLA, horizontal axis view. Other abbreviations as in previous figures

• 

  Figure 4. [68Ga]Ga-RGD uptake in the anterior wall of the LV after one week (A) and four weeks (B). The uptake is higher after one week, but there is no difference between the MI groups between week one and week four. There is a positive correlation between EDV at four weeks and uptake of [68Ga]Ga-RGD after one week (C). There is a negative correlation between EF at four weeks and uptake of [68Ga]Ga-RGD after one week (D). EDV, end diastolic volume; EF, ejection fraction; FU, follow-up. Other abbreviations as in previous figures

• 

  Figure 5. Flow cytometry evaluation of heart after MI. Cellular composition of hearts (A). Positivity of αv and β3 of all cells in hearts (B). αv and β3 expression on endothelial cells (C), myocytes, and immune cells. Correlation of [68Ga]Ga-RGD uptake to αv on endothelial cells, myocytes and immune cells (D). n = 12 one week after MI, n = 12 four weeks after MI and n = 10 for sham. Statistical differences were determined using mixed-effect analyses with Dunnetts correction for multiple comparisons to sham in A–C and pearsons correlation in D. MI, myocardial infarction; %ID/g, % injected dose per gram tissue. Other abbreviations as in previous figures

• 

  Figure 6. Histological verification of infarction after one and four weeks. The staining for Masson’s trichrome shows a fibrotic area corresponding to the accumulation of [68Ga]Ga-RGD pictured with autoradiography. MT, Masson’s Trichrome; HE, Hematoxylin & Eosin; AR, autoradiography

• 

  Figure 7. Masson’s trichrome staining shows a clear area of fibrosis compared to healthy tissue (A, B). The immunohistochemically staining for integrin β3 shows an accumulation in the vessel wall (C). The quantification of fibrotic tissue on MT shows a significant difference between sham and the MI groups (D). The extent of fibrosis is unchanged between week 1 and 4 in the MI group, indicating a stable and consistent ligation of the LAD