A NOVEL SITE-TARGETED ULTRASONIC CONTRAST AGENT WITH BROAD BIOMEDICALAPPLICATION

Background In this work, we report a novel targetable ultrasonic contr ast agent with the potential noninvasively define and localize myriad pathological tissues for diagnosis or therapy. The agent is a biotinyl ated, lipid-coated, perfluorocarbon emulsion that has low inherent ech ogenicity unless bound to a surface or itself. Methods and Results In study 1, emulsions with and without biotin were suspended in buffered saline and imaged with a 7.5-MHz linear-array transducer. Neither emul sion manifested significant ultrasonic backscatter until avidin was ad ded. Avidin-induced aggregation produced a marked enhancement in backs catter from the biotinylated but not from the control emulsion. In stu dy 2, porcine fibrin clots in vitro were pretargeted with biotinylated antifibrin monoclonal antibodies and then exposed to avidin and then to biotinylated or control perfluorocarbon emulsions. The basal acoust ic reflectivity of clots imaged with a 7.5-MHz linear-array transducer was uniformly low and was increased substantially by exposure to the targeted biotinylated emulsion. In study 3, partially occlusive arteri al thrombi were created in dogs and then exposed to antifibrin antibod ies and avidin in situ. Biotinylated or control emulsion was administe red either in situ or systemically. At baseline, all thrombi were unde tectable with a 7.5-MHz linear-array transducer. Thrombi exposed to an tifibrin-targeted contrast exhibited increased echogenicity (P<.05); c ontrol thrombi remained acoustically undetectable. Conclusions These d ata provide the first in vivo demonstration of a site-specific ultraso nic contrast agent and have potential for improved sensitivity and spe cificity for noninvasive diagnosis of thrombi and other pathological d iseases.