Comparison of fluorescence-labeling strategies of colon cancer for fluorescence-guided surgery of liver metastasis in orthotopic mouse models

The goal of three studies was to determine if fluorescence-guided surgery (FGS) could be an improvement over standard bright-light surgery (BLS) in experimental colon cancer liver metastasis nude mouse models. In one study an orthotopic mouse model of human HT-29-green fluorescent protein (GFP)-expressing colon cancer liver metastasis was established, and mice were randomized into FGS or BLS groups. FGS was performed using a handheld portable fluorescence imaging system to visualize the metastasis during surgery. The FGS-treated mice had significantly prolonged disease-free survival (DFS) and overall survival (OS) compared to BLS-treated mice. In another study, we used the telomerase-dependent GFP-containing adenovirus OBP-401 to label colon cancer liver metastasis in situ in an orthotopic mouse model. OBP-401-GFP-labeled liver metastasis could be completely resected with FGS. In contrast, BLS could not effect a complete resection. OBP-401-FGS reduced the recurrence rate and prolonged OS compared with BLS. In another study an orthotopic mouse model of colon cancer liver metastasis expressing GFP was subsequently labeled with anti-CEA antibody conjugated to DyLight 650. Mice underwent BLS or FGS with anti-CEA-DyLight 650. Mice that underwent FGS had a significantly smaller area of residual tumor and significantly longer DFS and OS. This series of experiments obtained with an orthotopic models of colon cancer liver metastasis suggest that FGS can benefit resection of this recalcitrant disease in the clinic.