Abstract 12763: Ischemic Memory Imaging with a Selectin-targeted Microbubble Contrast Agent: Efficacy and Safety Testing in a Non-human Primate Model of Myocardial Ischemia
Background: Molecular imaging of P-selectin with targeted myocardial contrast echocardiography (MCE) has been demonstrated in rodent models to accurately detect recent ischemia. The aim of this study was to develop a targeted contrast agent designed for human use and to test its safety and efficacy in a closed-chest primate model of brief ischemia.
Methods: Anesthetized adult rhesus macaques were studied and were randomized to a non-ischemic control group (n=3), or myocardial ischemia group (n=6). Ischemia was produced by percutaneous balloon catheter occlusion of the LAD or left circumflex for 5 min, during which risk area (RA) was measured by MCE perfusion imaging. Selectin-targeted MCE was performed at 30 and 90 min after reperfusion, or at similar time intervals in controls, using a lipid microbubble bearing a covalently-attached dimeric recombinant form of human p-selectin glycoprotein ligand-1 (MB-YSPSL). Collection of blood for a safety panel, electrocardiography, and echocardiography were performed at baseline, and before and after each targeted imaging acquisition. Myocardial infarction was excluded by MCE perfusion imaging.
Results: Intravenous injection of MB-YSPSL did not alter vital signs, O2 saturation, ECG, or any of the serum safety markers (C', troponin, coagulation assays, etc.). On echocardiography, MB-YSPSL did not acutely affect chamber size, Doppler and 2-D parameters of LV and RV systolic function, or pulmonary vascular resistance. Reversible LV dysfunction occurred in the RA and also in the remote territory in some animals during acute ischemia. On targeted MCE, MB-YSPSL produced strong signal enhancement in the post-ischemic RA at 30 min (25±11 IU) and 90 min (13±3 IU) after reflow, and was greater (p<0.05) than in the remote territory (11±4 and 3±2 IU, at 30 and 90 min). There was no enhancement (<1 IU) seen in control animals. There was no evidence for myocardial infarction on MCE at protocol completion.
Conclusions: Molecular imaging with a selectin-targeted microbubble bearing a small molecule selectin ligand is both safe and effective for imaging recent myocardial imaging in primates. This technique may provide a method for the detection of recent or ongoing ischemia in patients with chest pain even in the absence of necrosis.
- © 2010 by American Heart Association, Inc.