In vitro characterization of liposomes and Optison® by acoustic scattering at 3.5 MHz

Liposomes are phospholipid vesicles that can encapsulate both gas and fluid. With antibody conjugation, new formulations, known as immunoliposomes, can be targeted to atheroma and other pathologic components and are, thus, being developed as novel diagnostic ultrasound (US) echo contrast agents to enhance atherosclerosis imaging. The majority of these echogenic liposomes range in diameter from 0.25 to 5.0 mum. To quantify the echogenicity of liposome suspensions of varying concentrations, the backscattering coefficient at 3.5 MHz was determined experimentally. The backscattering coefficient was also estimated theoretically as a function of air volume fraction by modeling the encapsulated air as a free air bubble and assuming single bubble scattering. For most of the liposome concentrations examined in this study (on the order of 10(8)/mL), the backscattering coefficient equals or exceeds that of Optison(R) at the human clinical dosage (on the order of 10(4)/mL). Experimental measurement of the decrease in backscattering coefficient shows promise as a sensitive method for determining whether liposomes are left intact or destroyed during imaging; thus, helping to explore their potential as a vehicle for targeted drug delivery. In addition, the attenuation of US through liposome suspensions is negligible at 3.5 MHz relative to the attenuation through Optison(R) (0.25 dB/cm), suggesting that liposomes have a much higher scatter-to-attenuation ratio and could be more efficient as contrast agents.