PHYSICAL AND BIOCHEMICAL-CHARACTERIZATION OF ALBUNEX(TM), A NEW ULTRASOUND CONTRAST AGENT CONSISTING OF AIR-FILLED ALBUMIN MICROSPHERES SUSPENDED IN A SOLUTION OF HUMAN ALBUMIN

Albunex(TM) is a new ultrasound contrast agent for medical imaging. Th e product consists of air-filled albumin microspheres suspended in a s olution of 5% (w/v) human albumin. The suspension is sterile, non-pyro genic and isotonic, with a pH of 7.0 and a viscosity of 1.4 relative t o water. The contrast effect is caused by the air-filled microspheres, which range in diameter from 1 to 15 mum, with less than 5% being lar ger than 10 mum. The product contains a total of about 7 x 10(8) micro spheres/ml of suspension. The number concentration of microspheres wit h diameters between 4 and 10 mum is about 2 x 10(8)/ml. The latter mic rosphere traction is assumed to give the main contribution to the ultr asound signal in the left ventricle of the heart after intravenous inj ection. The air-filled microspheres are prepared by sonication of a he ated solution of 5% (w/v) human albumin. During the sonication process , microbubbles of air are formed which become encapsulated in a thin s hell of aggregated albumin about 15 nm in thickness. Due to the stabil izing effect of the albumin shell, the air-filled microsphere suspensi on is stable for at least 2 years when stored refrigerated. The micros phere protein represents about 1.5% of the total protein in the suspen sion. The remaining protein is soluble albumin molecules which behave like the albumin molecules in the starting material when analysed by a number of biochemical techniques.