Abstract 15086: Early 18F-galacto-RGD Uptake and Left Ventricular Remodeling in a Rat Model of Myocardial Infarction
Objectives: 18F-Galacto-RGD is a PET tracer that binds to βvβ3 integrin receptors. Expression of βvβ3 integrin is increased after myocardial infarction (MI) as part of the healing process, but its relationship to subsequent left ventricular (LV) remodeling is unknown. Therefore, we studied whether early myocardial 18F-Galacto-RGD uptake is associated with long-term LV remodeling after MI in rat.
Methods: The study group consisted of 31 rats with MI verified by histology (permanent left coronary artery ligation) and 9 sham-operated controls. Rats (n=25) were imaged with small animal PET scanner 90–120 minutes after injection of 1 mCi of 18F-Galacto-RGD 1 week post-MI. Myocardial perfusion scan with 13N-ammonia was done to define infarcted area 1 and 12 weeks post-MI. Magnetic resonance imaging (MRI) using 1.5T scanner and small animal coil was used to measure LV end-diastolic and systolic volumes (EDV and ESV) repeatedly 1 and 12 weeks post-MI. In 6 rats 18F-Galacto-RGD uptake was verified by autoradiography 1 week post-MI.
Results: Average 18F-Galacto-RGD uptake was higher in the infarcted area than in the remote myocardium of MI rats or in controls 1 week post-MI (0.20±0.05 vs. 0.06±0.03 and 0.07±0.04 %ID/cc, respectively, p<0.001). Autoradiography of tissue sections confirmed 18F-Galacto-RGD uptake that correlated with capillary and macrophage densities (r=0.82, p<0.001 and r=0.47, p=ns). 18F-Galacto-RGD uptake in the infarcted area inversely correlation with an increase in perfusion defect size from 1 to 12 weeks post-MI (r=-0.61, p<0.001). LV EDV and ESV increased and EF remained low from 1 to 12 weeks post-MI by MRI. Average 18F-Galacto-RGD uptake in the defect area was significantly lower in rats with >20% than <20% increase in EDV from 1 to 12 weeks (0.15±0.07 vs. 0.21±0.05 %ID/cc, n=10 and 15, p<0.05). Furthermore, 18F-Galacto-RGD uptake in the defect area showed an inverse correlation with change in EDV (r=-0.61, p<0.001) and ESV (r=-0.56, p<0.01).
Conclusions: Low level of 18F-Galacto-RGD uptake early after MI predicted significant LV remodeling at 12 weeks post-MI. This suggests that βvβ3 integrin expression plays a role in myocardial repair after MI and enables monitoring by molecular imaging with possible prognostic information.
- © 2010 by American Heart Association, Inc.