Abstract 1409: Molecular Imaging of Post-Infarction Cardiac Remodeling and Effects of Anti-Angiotensin Therapy

Background. Collagen deposition and interstitial fibrosis contribute to development of cardiac remodeling and heart failure (HF) after myocardial infarction (MI). We used Tc-99m-labeled Cy5.5-RGD imaging peptide (CRIP), for molecular imaging of the extent of collagen deposition. Methods. Of 46 Swiss-Webster mice, (MI) was induced in 41 by left coronary artery occlusion and 5 mice were imaged unmanipulated. Of these, 6, 6, and 5 mice, received intravenous CRIP for micro-SPECT/micro-CT imaging in vivo after 2, 4, and 12 weeks of MI. Eight mice received captopril or captopril with losartan for 4 weeks following MI before CRIP imaging for the assessment of effect of anti-angiotensin therapy on collagen deposition. To evaluate the specificity of the probe, 6 animals received scrambled peptide 4 weeks after MI. The remaining 10/46 mice, received CRIP without a radiolabel after 2 weeks of MI for histological characterization of tracer uptake by two-photon microscopy. Results. Distinct myocardial CRIP uptake was observed in the infarct area and border zone. The quantitative uptake in the infarct area, expressed as percent injected dose per gram (%ID/g), was highest in mice at 2 weeks (2.75±0.46%), followed by 4 (2.26±0.09%), and 12 weeks (1.74±0.24%) after MI as compared to uptake in sham-operated mice (0.59±0.19%). In the peri-infarct and remote areas, the uptake was higher at 12 weeks. The histologic characterization revealed specificity of the probe for replacement, interstitial and perivascular fibrosis. Captopril (1.78±0.31%) and combination of captopril and losartan (1.13±0.28%) significantly decreased radiotracer uptake in the infarct. The uptake of scrambled peptide (0.74 ±0.17%) was similar to CRIP uptake in normal myocardium. Conclusions. Radiolabeled CRIP allows for noninvasive visualization of interstitial alterations during cardiac remodeling. The CRIP uptake is significantly reduced with captopril and losartan treatment. If proven clinically feasible, such a strategy would help identify and prevent evolution of heart failure in post-MI patients.