Site targeted acoustic contrast agents are now being developed in commercial and academic laboratories. We have recently demonstrated a lipid encapsulated, nongascous, perfluorocarbon microemutsion which can enhance the ultrasonic image of thrombi when administered in situ. The perfluorocarbon contrast system utilizes avidin-biotin interactions to conjugate a pretargeted biotinylated ligand to the biotinylated acoustic particle. Although antibodies have been given systemically in a variety of animal models and in humans to successfully target isotopes, drugs or toxins, no particulate agents, such as those needed for ultrasonic contrast, have been actively, targeted systemically to a pathological tissue, such as thrombus. The objective of this study was to demonstrate an increased sensitivity of thrombosis detection with ultrasound following intravenous administration of a targeted contrast system. In eight dogs, partially occlusive, external carotid thrombi, created by electrical current injury, were exposed in situ to biotinylated antifibrin monoclonal antibodies and avidin and ther acoustically enhanced following systemic administration of the targeted perfluorocarbon emulsion. Ultrasonic imaging was performed before and during contrast administration with a 7.5 MHz linear phased array transducer. Serial blood perfluorocarbon concentrations were measured. Increased acoustic reflectivity was noted within 5 to 10 minutes after the systemic injection of the perfluorocarbon emulsion and clear, morphologic delineation of the thrombi was achieved within 30 minutes. Pixel gray scale levels of the targeted thrombi (97.5 ± 5.91 were increased (p<.05) in comparison with the lumen (3.5 ± 0.9).The pharmacokinetics of the perfluorocarbon particles revealed that blood perfluorocarbon concentrations decreased along a classic, two-compartment biexponential decay model with a half-life of 64 ± 3.5 minutes. These data demonstrate a fibrin-specific ultrasonic contrast agent administered intravenously and suggest the potential for improved diagnosis of thrombi in patients with deep vein thrombosis, pulmonary embolism or stroke.
|Number of pages||1|
|Journal||Journal of the American Society of Echocardiography|
|State||Published - Dec 1 1997|