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Abstract #0588

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

1Radiology, Medical School of Johns Hopkins Univ., Baltimore, MD, USA

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.