DEVELOPMENT OF A STABLE ULTRASOUND CONTRAST AGENT

UNTIL RECENTLY, CARDIAC ULTRASOUND HAS OFFERED NO METHOD OF EVALUATING MYOCARDIAL PERFUSION OTHER THAN ASSESSMENT OF THEEND RESULTS OF ISCHEMIA, SUCH AS WALL MOTION ABNORMALITIES. RECENT ATTEMPTS AT DEVELOPING AN EFFECTIVE CONTRAST AGENT TO MEASURE MYOCARDIAL PERFUSION HAVE RESULTED IN THE DEVELOPMENT OF MICROBUBBLES, UNSTABLE PREPARATIONS OF AIR TRAPPED IN FLUID WHICH SERVE AS HIGHLY ECHOGENIC MEDIA. CLINICAL UTILITY OF CONTRAST ULTRASONOGRAPHY FOR MEASURING BLOOD FLOW IS CRITICALLY DEPENDENT ON THE DEVELOPMENT OF STABLE MICROBUBBLES THAT ARE SMALL ENOUGH FOR UNHINDERED CAPILLARY PASSAGE FOR INTRAVENOUS INJECTION. THE PHASE I GOAL IS TO DEVELOP REPRODUCIBLE, STABLE, SMALL, AIR-TRAPPED SPHERES TO SERVE AS A PERFUSION CONTRAST AGENT. THE AGENT WILL OPTIMALLY CONSIST OF 2.0-MICRON-DIAMETER, AIR-TRAPPED SPHERES, WHICH WILL BE TESTED FOR SHELF-LIFE AND ECHOGENIC PROPERTIES. WHEN STABLE PREPARATIONS ARE MADE, TESTS WILL BE PERFORMED BOTH IN VITRO AND IN VIVO TO DEMONSTRATE CONTRAST EFFICACY. THE RESULTS OF PHASE I WILL SERVE AS A BASIS DURING PHASE II TO PERFORM FULL TOXICITY TESTING IN RODENTS AND DOGS. AFTER SUCCESSFUL COMPLETION OF TOXICITY TESTING, AN INVESTIGATIONAL NEW DRUG (IND) APPLICATION WILL BE FILED AND CLINICAL EVALUATION PERFORMED TO OBTAIN FOOD AND DRUG ADMINISTRATION APPROVAL. SUCCESSFUL DEVELOPMENT OF A STABLE ULTRASOUND CONTRAST AGENT WILL HAVE WIDE APPLICABILITY, NOT ONLY IN MONITORING CARDIAC PERFUSION BUT ALSO IN THE ASSESSMENT OF TISSUE PERFUSION IN OTHER ANATOMIC SITES.