Fluorescent Anti-CEA Antibody Detects Submillimeter Colon Cancer Metastases

SGM-101, a near-infrared 700 nm emitting fluorophore-conjugated antibody targeting carcinoembryonic antigen, has shown promise in colorectal cancer (CRC) imaging. The present study determines whether colocalization of SGM-101 fluorescence excited at 700 nm and tumor luciferase expression can detect colon cancer micrometastases in orthotopic nude mouse models using the Pearl small animal preclinical imaging system and an FDA-approved (U.S. Food and Drug Administration) Arthrex Synergy Vision and exoscope clinical imaging system.

LS174T-luciferase human CRC cells were implanted in athymic mice to establish subcutaneous (n = 4) and orthotopic (n = 8) tumor models. Mice received 60 μg of SGM-101 intravenously 72 h prior to imaging and 4.5 mg of D-luciferin via intraperitoneal injection 10 min before imaging. Imaging was performed with the Pearl Trilogy System and the Arthrex Synergy Vision System and exoscope to detect SGM-101 tumor labeling and luciferase expression, including primary tumors and micrometastases. Colocalization of SGM-101 tumor labeling was determined by calculating tumor-to-background fluorescence ratios (TBRs). Biodistribution analysis and histologic confirmation were performed postmortem.

SGM-101 fluorescence colocalized with tumor luciferase in both subcutaneous and orthotopic tumor models. Subcutaneous tumors showed TBRs of 3.54 and 2.51. Orthotopic tumors demonstrated strong labeling with an average TBR of 5.24 (±0.93). Microscopic peritoneal wall metastases (<1 mm) were detected by luciferase expression and SGM-101 fluorescence with both preclinical Pearl and clinical Arthrex imaging systems. Colocalization and biodistribution studies confirmed high tumor-specific uptake, with background signal found primarily in the liver. The Arthrex exoscope enabled clear real-time detection in the 700 nm channel, indicating that SGM-101 has clinical potential to detect primary colon cancer and metastatic tumors.

The present study demonstrates that SGM-101 enables high-contrast tumor detection in CRC models and colocalizes with tumor luciferase expression and was able to detect colon cancer micrometastases ˂1 mm. The present findings suggest that SGM-101 labeling of tumors can be detected by preclinical as well as clinical imaging systems, demonstrating clinical potential for tumor staging and fluorescence guided surgery in the future.