Molecular imaging of alphaVbeta3 integrin for evaluation of myocardial injury after acute myocardial infarction

Abstract

Abstract Background 68Ga-NODAGA-RGD is a positron emission tomography (PET) tracer targeting αvβ3 integrin that is upregulated during angiogenesis. αvβ3 integrin expression increases early after acute myocardial infarction (AMI), and has been proposed as a marker of myocardial repair. Purpose We prospectively evaluated the uptake of 68Ga-NODAGA-RGD and its association to left ventricular function after human AMI. Methods Thirty patients underwent PET at 7.7±3.8 days after primary percutaneous coronary intervention for ST-elevation AMI. Resting myocardial perfusion was evaluated using 15O-water PET followed by evaluation of 68Ga-NODAGA-RGD uptake 60–75 minutes after injection of 179 MBq of tracer. Left ventricular function was evaluated by transthoracic echocardiography on the day of PET, and at 6-month follow-up. The definition of the ischemic area at risk and remote myocardial segments was based on the culprit coronary arterial segments in invasive angiography. 68Ga-NODAGA-RGD images were co-registered with perfusion images and uptake was measured as the standardized uptake value in the segment with the highest uptake (SUVmax) in ischemic area at risk, and the mean standardized uptake value (SUVmean) in remote segments. In addition, we calculated 68Ga-NODAGA-RGD uptake corrected to the mean myocardial blood flow (MBF) in the area at risk (SUVmax/MBFmean) to account for reduced distribution of tracer in non-viable tissue. Results Mean age of patients was 64±9 years, and 90% were males. Uptake of 68Ga-NODAGA-RGD was low in the remote myocardium, but focally increased in the ischemic area at risk (Figure 1). SUVmax in the ischemic area at risk was higher than SUVmean of the remote myocardium (0.73±0.16 vs. 0.51±0.11, p<0.001). 68Ga-NODAGA-RGD SUVmax did not correlate with MBF in the area at risk. Univariable predictors of 68Ga-NODAGA-RGD SUVmax in the area at risk included peak Troponin T (p<0.001), peak pro-BNP (p<0.001), low global longitudinal strain (p=0.01), and low regional longitudinal strain in the area at risk (p=0.02). In multivariable analysis, peak pro-BNP independently predicted SUVmax in the area at risk (p<0.001). At follow-up, left ventricular ejection fraction increased by 1.6±6.9% and global longitudinal strain by 0.5±3.2%. In univariable analysis, SUVmax and SUVmax/MBFmean in the area at risk predicted improvement of global longitudinal strain at 6 months after AMI (p=0.04 and p<0.001, respectively). Conclusion 68Ga-NODAGA-RGD uptake shows increased αvβ3 integrin expression in the ischemic area at risk early after reperfused AMI that is associated with the extent of myocardial injury, both regional and global systolic dysfunction, and increased left ventricular filling pressure. Increased 68Ga-NODAGA-RGD uptake in ischemic myocardium at risk predicts left ventricular function improvement at 6 months after AMI. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Academy of Finland, Finnish Foundation for Cardiovascular Research