Color-coded double labeling of colon-cancer liver metastasis and adjacent liver segment for image guided metastasectomy: A proof-of-concept review of clinical translatability

Background: Colon-cancer liver metastases is the frequent cause of death due to difficulties in visualizing margins of the metastases resulting in incomplete resection. To perform safer and more reliable liver surgery, indocyanine green (ICG) labeling has been used to visualize liver tumors and liver segment, but it is difficult to distinguish between a liver metastasis and its adjacent liver segment with traditional use of ICG alone. We have previously developed a method to label a liver metastasis with a tumor-specific fluorescent conjugated antibody and the adjacent liver segment with ICG in order to perform image guided metastasectomy. Methods: Nude mice were surgically orthotopically implanted with a human colon-cancer cell-line or colon-cancer liver metastases derived from patients. After liver tumor growth, mice received near-infrared conjugated anti-CEA or anti-CEACAM antibody to label the liver metastases. ICG was intravenously injected after ligation of the left or left lateral Glissonean pedicle resulting in specific labeling of the segment adjacent to the tumor with preserved blood-flow in the liver. Imaging was performed with the FLARE Imaging Systems. Results: The liver metastasis was brightly labeled with near infrared fluorescence with selective tumor targeting by the fluorescent anti-CEA or anti-CEACAM antibody, which was imaged on the 700 nm channel. The adjacent liver segment with preserved blood-flow in the liver had a bright fluorescence ICG 800 nm signal, while the left or left lateral segment had no fluorescence signal. Overlay of the images showed clear color-coded differentiation between the tumor and the liver segment, enabling image guided metastasectomy. Conclusions: Color coded imaging of the liver metastasis and adjacent liver segment in the present review can be used in the future for improved liver metastasectomy in the clinic.