MR agent targets PE-CAM-1 molecule to see transitory myocardial infarction

CONTEXT: In acute myocardial infarction (AMI), the culprit thrombus sometimes dissolves before the patient arrives in the emergency room, leaving the cardiologist with few clues as to the source of the chest pain. A new iron oxide-labeled "ischemic memory agent" may make it possible to use cardiac MR to identify myocardium that has been temporarily deprived of blood and oxygen. These findings were reported at the 2006 Society for Cardiovascular Magnetic Resonance meeting by Brent A. French, Ph.D., an associate professor of biomedical engineering at the University of Virginia, Charlottesville.

RESULTS: French used a rat monoclonal antibody targeted against mouse platelet-endothelial cell adhesion molecule-1. PE-CAM-1 is located in the endothelial junction between cells. After a heart attack, damaged endothelial cells are believed to retract, exposing the junctional molecule and making it an ideal marker for ischemia and infarction.

Investigators surgically induced AMI in six mice. After myocardial reperfusion, three mice were injected intravenously with the PE-CAM-1-targeted monoclonal antibody, which had been conjugated to Feridex. Three mice were injected with a Feridex-labeled immunoglobulin molecule. An hour later, all mice underwent cardiac MR imaging with an electrocardiographically gated, 2D cine FLASH sequence on a 4.7T scanner.

The UVA researchers found that the PE-CAM-1-targeted contrast agent homed to areas of myocardial ischemia, an observation that was confirmed by histopathology.

IMAGE: There is no evidence of the contrast agent in the mice injected with immunoglobulin (A). In the mice injected with the PE-CAM-1-targeted contrast agent (B), MRI demonstrates hypointense speckles in the anterolateral wall of the left ventricle that correspond to the white infarct zone on histologic staining (C).

IMPLICATIONS: Using a PE-CAM-1-targeted contrast agent, cardiac MR could guide interventional treatment of patients with a stuttering type of acute MI. French expects to begin studying the use of the contrast agent in identifying jeopardized myocardium in a mouse model of unstable angina.