Abstract 9453: Dual Probe Hybrid Molecular PET/MR Imaging of Post-infarct Myocardial Inflammation and Healing

Abstract

Background: Myocardial infarction elicits a strong inflammatory response, with profound recruitment of innate immune cells. The magnitude of inflammation influences infarct size and severity of post-MI ventricular dysfunction. Inflammatory monocytes and macrophages produce substantial amounts of myeloperoxidase (MPO), which leads to oxidative stress. In addition, plasma transglutaminase factor XIII (FXIII) plays a key role in wound healing, via its contribution to extracellular matrix organization. Thus, we hypothesize that targeted molecular imaging of FXIII and MPO activity using a hybrid PET/ MRI approach will enable simultaneous in vivo assessment of infarct healing and post-infarct inflammation. Methods and Results: To assess in vivo FXIII activity, we developed a fluorine-18 labeled affinity peptide (18F-FXIII), with a blood half-life of 13.3 min, using a facile ‘click-chemistry’ approach. FXIII recognizes the PET probe as a substrate and cross-links it to extracellular matrix proteins, leading to local entrapment within the healing infarct. 18F-FXIII and gadolinium-based activatable sensor of MPO activity (MPO-Gd) were injected in C57BL/6 mice on day 4 after permanent coronary ligation. PET/MR imaging was performed and fusion was facilitated using external fiducial markers. 18F-FXIII uptake in the heart was significantly higher in animals with MI as compared to controls, as measured by scintillation counting (percent injected dose per gram tissue 0.29±0.01 vs 0.17± 0.03, p<0.03). On autoradiography, 18F-FXIII uptake correlated well with infarct area on TTC staining. PET/MR imaging allowed for simultaneous in vivo assessment of MPO and FXIII activity (Figure). Conclusion: Dual probe hybrid PET/MR imaging with 18F-FXIII and MPO-Gd allows non-invasive assessment of post-infarct myocardial inflammation and infarct healing.