A new locoregional mouse model of gastric cancer for identifying probes for fluorescence guided surgery.

Background: In gastric cancer, the only opportunity for a cure is with surgical resection. Fluorescence-guided surgery is an emerging field that has the potential to improve rates of R0 resections. Mouse models with patterns of disease spread that would be deemed operable in patients are required for the testing of potential fluorescence-guided surgery probes.

Methods: One million cells of the human gastric cancer cell line MKN45 were suspended in 50 μL of phosphate-buffered saline and Matrigel and injected into the mouse stomach with a 29-gauge needle. After 8 to 12 weeks of tumor growth, mice were killed and laparotomy was performed to determine rates of tumor engraftment, local or distant spread, and involvement of celiac lymph nodes. For tumor labeling, mice were randomized to receive intravenous injection of an anti-CEA antibody (M5A), or IgG as a control, conjugated with the near-infrared dye IRDye800CW. Fluorescence imaging was performed using the LI-COR Pearl Imaging System 72 hours later.

Results: Infiltrative tumors were identified in 76.5% (n = 34) of mice. Intra-abdominal or peritoneal metastases were seen in 23.5% and carcinomatosis was seen in 5.9% of mice. Celiac lymph node metastases were seen in 55.5% of mice. M5A-IR800 administration resulted in bright labeling of primary tumors and metastatic celiac lymph nodes. Hematoxylin and eosin staining demonstrated incorporation of the gastric cancer cells throughout the layers of the mouse stomach and the presence of metastatic gastric cancer cells in celiac lymph nodes.

Conclusion: This new locoregional mouse model can be used to validate additional agents for their use in fluorescence guided surgical resection of gastric cancer.