Abstract. Background Fluorescence-guided surgery (FGS) of cancer is an emerging technology. Our laboratory has pioneered mouse models using fluorescent proteins, as well as fluorescent antibodies, to label tumors for FGS (1-11).To achieve complete tumor resection, it is necessary to understand the relationship between cancer cells and stromal cells in the tumor microenvironment (TME) (9). We previously reported imaging of the TME during tumor progression and metastasis by color-coding cancer and stromal cells (12-27).We have subsequently used genetic reporters to color code cancer and stroma cells in a patient-derived orthotopic xenograft (PDOX) model. Cancer cells were labeled with a telomerasedependent green fluorescent protein (GFP)-containing adenovirus (OBP-401) in a pancreatic cancer PDOX. The PDOX was labeled in the stroma by red fluorescent protein (RFP) during growth in transgenic mice that express RFP (9).In the present report, we developed a color-coded syngeneic model for FGS using a mouse lymphoma cell line (EL-4), expressing RFP, and transgenic C57/B6 mice ubiquitously expressing GFP under the control of the chicken β-actin promoter and cytomegalovirus enhancer. Using the portable, hand-held Dino-Lite fluorescence microscope, the EL-4-RFP tumor in the GFP mouse was color-coded imaged in order to visualize the tumor and TME and resected by FGS. Confocal microscopy of the resected tumor demonstrated that both tumor and the TME were completely resected by color-coded FGS. In the resected RFP-expressing tumor, various types of GFPexpressing stromal cells were observed intermingling with the cancer cells in the TME.
4443