Gas‐filled liposomes as ultrasound contrast agents for blood pool, thrombus‐specific and therapeutic applications

Our group has developed technology for stabilizing microbubbles with phospholipid coatings (Aerosomes®‐ImaRx Pharmaceutical Corp.). The first agent (MRX‐115) is based upon lipid‐coated microspheres filled with perfluoropropane gas and is in phase III clinical trials (October, 1997) for radiology and cardiology applications. Myocardial perfusion studies show the potential for the agent to detect ischemia in patients with myocardial infarcts. Targeting ligands have been covalently bound to lipids and incorporated into the stabilizing shells on the microbubbles. The first targeted agent planned for clinical trials is MRX‐408 (perfluorobutane gas, linear hexapeptide‐RGD analog). In vitro studies show enhanced visualization of thrombi, and in vivo studies in dogs with arterial and venous thrombi show selective enhancement, even in animals injected with heparin. In vitro studies have been performed to test sonothrombolysis comparing MRX‐115 to MRX‐408 with and without urokinase. The targeted contrast agent MRX‐408 increases the rate of clot dissolution with ultrasound. Targeted, tissue‐specific agents are feasible for ultrasound. A thrombus‐specific ultrasound contrast agent has the potential to improve clot characterization and detection as well as clot lysis.