Ultrasound and microbubble mediated Doxil delivery in a murine breast cancer model: Therapeutic efficacy dependence on tumor growth rate

The effect of tumor growth rate and treatment repeats are examined as parameters in pressure-mediated ultrasound treatments with microbubbles and Doxil in a murine breast cancer model. For this purpose, mice with a tumor doubling time of 8 and 13 days respectively received either a single or two ultrasound treatments (at 1 MHz/1 MPa) in conjunction with Definity microbubbles (1:1 dilution) and Doxil (3 mg/Kg dose) after the tumor size reached 150 mm³. The tumor model was generated using MDA-MB-231-luc cells implanted into the lower mammary fat pad of SCID beige mice. At 15 days post-treatment, tumor size was reduced by 3±18%, 8±14%, and 20±10% as compared to control for the Doxil only, ultrasound + microbubbles + Doxil (single treatment), and ultrasound + microbubbles + Doxil (2 treatments) groups, respectively, in the mice with the slower growing tumors. The mice with the faster growing tumor yielded tumor size reductions of 46±27%, 71±10%, and 61±26%, respectively, for the same groups. We hypothesize that treatment efficacy is dependent on the dynamics of the tumor itself, even within the same cell line.