The overall objective of this program is to synthesize a modified microbubble agent which is optimally suited for use in ultrasonic cavita- tion treatment of brain tumors. This development would facilitate further progress in developing therapeutic methodology for optimizing cavitation effects within (and hence destruction of) brain tumors, while minimizing heating damage in surrounding normal brain tissue. The specific objective of the (in vitro) Phase I program is to produce lipid-coated microbubbles (LCM) containing "pure" oxygen or other selected gases (instead of air). The modified LCM will be stabilized by a surfactant-coating containing an optimal combination of monoglycerides and cholesterol esters -- which can vary depending upon the encapsulated gas. The laboratory test program involves the determination (and comparison) of the average diameter, size distribution, concentration, and especially stability of microbubbles surrounded by the surfactant monolayer. The encapsulated gases to be employed individually are 02 , Ar, N2O, and CO2. The follow-on Phase II studies in animals would assess the likely enhanced cavitational (and direct chemical) effects of these modified LCM. If successful, such findings would allow development of a treatment modality useful for multiple and/or low-radiosensitivity intracranial tumors in humans.
