Targeting of the antivascular drug combretastatin to irradiated tumors results in tumor growth delay

Purpose. The aim of the study is to evaluate the effects of targeting the antivascular drug combretastatin to irradiated mouse melanomas. Methods. Combretastatin was incorporated into liposomes with surfaces modified by the addition of cyclo(Arg-Gly-Asp-D-Phe-Cys) (RGD) to create an immunoliposome (IL). This addition of RGD allows the liposome to be preferentially targeted to alpha(v)beta(3), an integrin up-regulated in the vasculature of irradiated tumors. C57BL mice bearing a transplanted B16-F10 melanoma were randomly assigned to one of the following treatment groups: untreated, a single dose of 5-Gy radiation (IR), IL (14.5 mg/kg of combretastatin), 5-Gy radiation plus IL, and a systemic administration of free drug (81.0 mg/kg of combretastatin). Results. In this transplanted tumor model, there was no significant increase in the volume of the IL + IR (5 Gy) treated tumors during the initial 6 days posttreatment; all other treatment groups exhibited exponential growth curves after day 3. The IL + IR (5 Gy) treatment resulted in a 5.1-day tumor growth delay compared to untreated controls. Conclusions. These findings indicate that preferential targeting of antivascular drugs to irradiated tumors results in significant tumor growth delay.