Clin Res Cardiol (2022). https://doi.org/10.1007/s00392-022-02002-5
Assessment of Porcine Coronary and Myocardial Inflammation Targeting P-selectin by Molecular MRI
T. Heidt1, J. Thielmann1, C. Weber1, T. Bühler1, D. Chiang-Jurado1, S. Reiss2, T. Lottner2, M. Bock2, C. Bode1, C. von zur Mühlen3
1Klinik für Kardiologie und Angiologie I, Universitäts-Herzzentrum Freiburg - Bad Krozingen GmbH, Freiburg im Breisgau; 2Albert- Ludwigs-Universität Freiburg, Freiburg im Breisgau; 3Innere Medizin III, Kardiologie und Angiologie, Albert- Ludwigs-Universität Freiburg, Freiburg im Breisgau;
Backgrounds: Inflammation is a hallmark of vulnerable atherosclerotic plaques and acute myocardial infarction. Magnetic resonance imaging (MRI) has a high diagnostic potential in cardiovascular disease due to the absence of ionizing radiation, 3D imaging capabilities, and superior soft tissue contrast compared to x-ray fluoroscopy. Molecular imaging further combines these advantages with target-specific contrast agents for functional assessment. In this project we aimed to non-invasively detect vascular and ischemic cardiac lesions in a porcine model using MRI and a molecular imaging contrast agent targeting the cell adhesion molecule p-selectin.


Methods/Results: To design a suitable contrast agent, monoclonal p-selectin antibody was functionalized with microparticles of iron oxide (MPIO). Specific binding of the contrast agent to the epitope of interest was confirmed by FACS and in vitro flow chamber with activated porcine coronary endothelial cells or platelets. In vivo, we established a coronary balloon stretch-injury model or used a closed-chest model of ischemia-reperfusion (I/R) by temporary coronary balloon-occlusion in juvenile farm pigs. After injury, animals were transferred into the MR system and the molecular contrast agent was selectively injected into the coronary artery using interventional MRI techniques. Stretch injury induced local overexpression of p-selectin, however missed detection by molecular imaging due to the unfavorable ratio of target area to local shear stress with insufficient contrast binding. Improving the ratio in a porcine model of I/R, we detected a specific contrast signal in the infarcted LV area that was absent in non-infarcted heart segments.   

Conclusion: Molecular MRI using target-specific contrast agents allows for detection of myocardial inflammation in a porcine model of I/R. Yet, the concept is not sensitive enough for non-invasive detection of localized vulnerable coronary lesions.
https://dgk.org/kongress_programme/jt2022/aP1239.html