IN-VITRO TARGETING OF ANTIBODY-CONJUGATED ECHOGENIC LIPOSOMES FOR SITE-SPECIFIC ULTRASONIC IMAGE-ENHANCEMENT

Tissue-specific ultrasonic enhancement can be used for the detection a nd characterization of atherosclerosis. We have previously demonstrate d the generation of inherently echogenic (acoustically reflective) lip osomes solely by varying lipid composition and controlling the method of production. In this study, echogenic liposomes composed of phosphat idylcholine (PC), 4-(p-maleimidophenyl) butyryl phosphatidylethanolami ne (MPB-PE), phosphatidylglycerol (PG), and cholesterol were conjugate d to human gamma globulin to determine the effect of antibody conjugat ion on liposomal acoustic reflectivity. The liposomes remained highly echogenic following antibody conjugation. Echogenic liposomes were als o conjugated to rabbit antihuman fibrinogen to study their ability to target fibrin. Antibody-conjugated liposomes were targeted to fibrin-c oated filter paper and slides, thrombi made in vitro, and segments of atheroma in an animal model of atherosclerosis. Liposomes were detecte d by scanning electron microscopy, radiolabeling, and imaging with int ravascular ultrasound. Electron microscopy revealed attachment of anti body-conjugated liposomes to fibrin on slides and to the fibrous plaqu es of the arterial segments, whereas unconjugated liposomes did not at tach. Similarly, conjugated liposomes did not attach to normal arterie s, indicating their binding to the arterial segment is directed toward s a component of the fibrous plaque. Ultrasound imaging of the thrombi demonstrated surface attachment of the acoustic conjugated liposomes. I-125-Labeled liposomes conjugated to rabbit anti-human were targeted to fibrin-coated paper. Counting specifically bound radioactivity sho wed that >84% of applied liposomes remained attached to the fibrin aft er washing with saline. These results demonstrate the potential of aco ustically reflective liposomes for site-specific targeting and acousti c enhancement.