Investigating vascular-targeting strategies with three-dimensional power Doppler ultrasound.

Abstract

Vascular targeting agents have been recently combined strategically with existing cancer therapies to potentially enhance tumor response. Our aim was thus to investigate the role of blood vessels in radiation response and how blood vessels can be targeted to enhance treatments. Breast cancer MDA-MB-231 xenografts were treated with single radiation doses of 0–16 Gy alone, or in combination with Sutent, an antiangiogenic agent. 3-D ultrasound tumor data were acquired before and 24 h after treatment using a 25-MHz transducer and a VEVO770. The vascularity index (VI) was used to quantify blood from power Doppler data, while quantitative ultrasound spectroscopy (QUS) was used to monitor tumor cell death. Staining using TUNEL and CD31 of tumor sections was used to measure cell death and tumor vasculature distributions. Preliminary results indicated a VI decrease of up to 50% when tumors were irradiated with 16 Gy. Sutent-radiation combination treatments showed an increase in the VI, which may be associated with a vascular normalization effect. Analyses with QUS and TUNEL staining indicate an enhanced dose-dependent increase in tumor cell death when radiation was combined with Sutent. These results indicate that Sutent treatment may radiosensitize tumors by altering the tumor microenvironment. [Work funded by the Canadian Breast Cancer Foundation.]