Molecular imaging of early α _vβ ₃ integrin expression predicts long-term left-ventricle remodeling after myocardial infarction in rats

¹⁸F-galacto-RGD ( ¹⁸F-RGD) is a PET tracer binding to α _vβ ₃ integrin receptors that are upregulated after myocardial infarction (MI) as part of the healing process. We studied whether myocardial ¹⁸F-RGD uptake early after MI is associated with long-term left-ventricle (LV) remodeling in a rat model. Methods: Wistar rats underwent sham operation (n = 9) or permanent coronary ligation (n = 25). One week after MI, rats were injected with ¹⁸F-RGD to evaluate α _vβ ₃ integrin expression using a preclinical PET system. In the same rats, LV volumes and defect size were measured 1 and 12 wk after MI by ¹³N-ammonia PET and MRI, respectively. Results: One week after MI, ¹⁸F-RGD uptake was increased in the defect area as compared with the remote myocardium of MI rats or sham-operated controls (percentage injected dose per cubic centimeter, 0.20 ± 0.05 vs. 0.06 ± 0.03 and 0.07 ± 0.04, P < 0.001). At this time, ¹⁸F-RGD uptake was associated with capillary density in histologic sections. Average ¹⁸F-RGD uptake in the defect area was lowest in the rats demonstrating greater than 20% relative increase in the LV end-diastolic volume from 1 to 12 wk (percentage injected dose per centimeter cubed, 0.15 ± 0.07 vs. 0.21 ± 0.05, P < 0.05). In a multivariable logistic regression analysis, low ¹⁸F-RGD uptake was a significant predictor of increase in end-diastolic volume (r = 0.51, P < 0.05). Conclusion: High levels of ¹⁸FRGD uptake in the perfusion defect area early after MI were associated with the absence of significant LV remodeling after 12 wk of follow-up. These results suggest that α _vβ ₃ integrin expression is a potential biomarker of myocardial repair processes after MI and enables the monitoring of these processes by molecular imaging to derive possible prognostic information.