Fibrin-targeted agent enhances detection of microthrombi of vulnerable plaque

CONTEXT: The rupture of atherosclerotic plaque, followed by the formation of an occlusive thrombus, causes nearly all heart attacks and many strokes. Multidetector CT has shown increasing success in the detection of arterial stenoses and differentiation of calcified and soft plaque. It has not, however, been able to detect an important early warning sign of plaque rupture: fibrin-rich microthrombi that develop within microfissures of vulnerable lesions. New research reported at the 2003 annual meeting of the Society for Molecular Imaging suggests that could change.

RESULTS: Patrick M. Winter, Ph.D., Dr. Samuel Wickline, and Dr. Gregory Lanza, of the cardiovascular division at Washington University in St. Louis, worked with researchers from the U.K. and the Netherlands to develop a radio-opaque nanoparticle contrast agent through use of a special iodinated oil. After demonstrating the inherent radio-opacity of the contrast material with CT imaging, they linked antifibrin monoclonal antibodies to the surface of the nanoparticles and added the preparation to plasma clots suspended in saline on a suture line. For comparison, nanoparticulate contrast material without antifibrin antibodies was added to identical plasma clot suspensions.

CT was far better at imaging thrombus when the contrast material consisted of fibrin-targeted nanoparticles: Gray-scale contrast enhancement was significantly greater with fibrin-targeted nanoparticles when compared to unaltered nanoparticles (210 vs. 160; p < 0.05). Contrast-to-noise ratios were markedly greater as well (22 vs. 5; p < 0.05).

IMPLICATIONS: This study shows for the first time that a fibrin-specific molecular imaging agent can increase the sensitivity of CT for the detection of thrombus. This technique may spur early detection and localization of vulnerable plaques, perhaps enabling their treatment during routine cardiac catheterization or intervention.