Heterogenous drug delivery in tumor leads to poor drug response, thus improving drug delivery can improve drug response. Previous studies have shown that modulating the tumor microenvironment can improve drug delivery and response. We hypothesize that radiation can increase drug delivery by modulating the tumor microenvironment. We propose to use a fluorescently labeled therapeutic antibody as an imaging tool to investigate drug delivery into head and neck cancer in a xenograft mouse tumor model.
Experimental design: We conducted an experiment examining drug delivery of Cetuxiumab-IRDye 800 (CTX-800) in a subcutaneous mouse model. Thirty mice were injected with SCC-47 in the flank. After the tumors had reached appropriate size, fifteen experimental mice were injected with .2 mg of CTX-800 and the radiated with 5gy. The fifteen control mice were injected with .2 mg of CTX-800, but did not receive radiation therapy. Three time points were examined 24, 48, and 72 hrs. At each time point tumors from five of the control mice and five of the experimental mice were imaged in vivo using the Pearl Imaging system. Immediately following imaging the mice from both the experimental and control group were sacrificed at each time point. The tumors and other organs were dissected and imaged using the Pearl imaging system to evaluate for fluorescence.
Results and Conclusion: Mean Fluoresce Intensity (MFI) was higher in the radiated mice compared to the non-radiated mice both in vivo and ex vivo. This suggests that radiation can increase drug delivery to tumors and has implications for timing of radiation and chemotherapy delivery.