Image-Guided Combined SiRNA and Enzyme/Prodrug Cancer Therapy

Cong Li¹, Marie-France Penet¹, Flonn Wildes¹, Tomoyo Takagi¹, Paul Winnard Jr. ¹, Dmitri Artemov¹, Zaver M. Bhujwalla¹

The ability to downregulate specific pathways that are overexpressed and critically important in cancer using small interfering RNA (siRNA) technology provides unprecedented opportunities to develop novel cancer-cell specific treatments. The ability to detect the delivery of the siRNA and combine it with the delivery of a chemotherapeutic agent primarily localized within the tumor would be of significant advantage in this quest. Here we have developed a prototype agent to image the delivery of a prodrug enzyme, bacterial cytosine deaminase, that converts a nontoxic prodrug 5-fluorocytosine to 5-fluorouracil, in combination with siRNA targeting of choline kinase, an enzyme critically important in breast cancer.