PARENT SESSION

Experimental and Clinical Therapeutics

(PP153) Targeting of the antivascular drug combretastatin to irradiated tumors results in tumor growth delay.

Pattillo, Christopher ^*,1, Sari-Sarraf, Farid¹, Nallamothu, Ramakrishna², Moore, Bob², Wood, George², Kiani, Mohammad^{1, 3}, ¹ Department of Mechanical Engineering, Philadelphia, PA, USA² Department of Pharmaceutical Science, Memphis, TN, USA³ Department of Radiation Oncology, Philadelphia, PA, USA

ABSTRACT- PURPOSE: To evaluate the effects of targeting the antivascular drug combretastatin to irradiated mouse melanoma and spontaneous mammary tumors. 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 v3, an integrin upregulated 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). Spontaneous mammary tumors in C3H/HeN mice were treated in a similar manner as above with IL to administer 12.0 mg/kg of drug and a single radiation dose of 10 Gy. RESULTS: In the transplanted tumor model group the IL+IR (5 Gy) treatment resulted in significant tumor growth delay compared to other treatment groups. Similar findings were observed in the spontaneous tumor model with a marked delay in tumor growth in the IL+IR group. Conclusions: These findings indicate that targeting of antivascular drugs to irradiated tumors results in significant tumor growth delay.

Key words: Antivascular drugs, targeted drug delivery, ionizing radiation, combretastatin