Fluorophore-conjugated anti-CEA Antibody for the Intraoperative Imaging of Pancreatic and Colorectal Cancer

Abstract

Introduction Colorectal and pancreatic cancers together comprise the third and fourth most common causes of cancer-related death in the United States. In both of these cancers, complete detection of primary and metastatic lesions at the time of surgery is critical to optimal surgical resection and appropriate patient treatment. Materials and Methods We have investigated the use of fluorophore-labeled anti-carcinoembryonic antigen (CEA) monoclonal antibody to aid in cancer visualization in nude mouse models of human colorectal and pancreatic cancer. Anti-CEA was conjugated with a green fluorophore. Subcutaneous, orthotopic primary and metastatic human pancreatic and colorectal tumors were easily visualized with fluorescence imaging after administration of conjugated anti-CEA. The fluorescence signal was detectable 30 min after systemic antibody delivery and remained present for 2 weeks, with minimal in vivo photobleaching after exposure to standard operating room lighting. Tumor resection techniques revealed improved ability to resect labeled tumor tissue under fluorescence guidance. Comparison of two different fluorophores revealed differences in dose–response and photobleaching in vivo. Conclusion These results indicate that fluorophore-labeled anti-CEA offers a novel intraoperative imaging technique for enhanced visualization of tumors in colorectal and pancreatic cancer when CEA expression is present, and that the choice of fluorophore significantly affects the signal intensity in the labeled tumor.

Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival

“…From a molecular-imaging perspective, ACPPDs have several advantages over other targeted fluorescent probes previously described in the literature for use in a surgical system (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Molecular fluorescence-guided surgery demands that a given probe (a), works for a wide variety of tumor types (b), offers ample signal with low background (c), binds tightly to the tumor, and (d), is not affected by the physical trauma of surgery.…”

“…Molecular fluorescence-guided surgery demands that a given probe (a), works for a wide variety of tumor types (b), offers ample signal with low background (c), binds tightly to the tumor, and (d), is not affected by the physical trauma of surgery. Although antibody approaches to fluorescence-guided surgery are attractive for individual tumor types that express unique surface markers such as colon (15), pancreas (16), or ovary (17), they are often not applicable to all tumor types. Most tumor antigens such as CEA and CA19-9 have no known etiological function, as demonstrated by their frequent elimination during passage in culture.…”

A Mouse Model of Fluorescent Protein-expressing Disseminated Peritoneal Lymphoma for Fluorescence-guided Surgery

“…The results of the present study suggest that FGS has clinical potential for peritoneally-disseminated cancer. The pioneering studies of our laboratories have demonstrated two strategies for labeling tumors for FGS: a telomerase-dependent adenovirus containing GFP (26) and a fluorescent conjugated tumor-specific antibody (27). FGS in now emerging in the clinic (28)(29)(30) and should become the standard paradigm in the near future.…”

Synthesis and characterization of bioactive conjugated near-infrared fluorescent proteinoid-poly(L-lactic acid) hollow nanoparticles for optical detection of colon cancer

“…As stated in the literature, CEA is upregulated on the mucosal side of LS174t colorectal cancer cell line, as opposed to SW480 (at least 10 3 less). 46 The concentration of biological ligand conjugated to the nanoparticles should be monitored carefully. The ligand content on the surface should be both sufficient for recognition by the cell from any angle of approach and and CEA] to a much higher extent than SW480 cells.…”