Detection of Metastatic Lesions in Esophageal Cancer Using a TROP2 Antibody‐Based Near‐Infrared Probe

Sacituzumab govitecan (SG), a trophoblast cell surface antigen 2 (TROP2)-targeting antibody-drug conjugate, is effective against solid tumors and a promising carrier for molecular imaging, yet its role in near-infrared (NIR) fluorescence imaging of metastases is unclear. Based on the dual rationale of frequent lymph node metastasis in esophageal squamous cell carcinoma (ESCC) and prevalent TROP2 overexpression, the IRDye800cw-labeled SG probe (SG-IR800) was evaluated for detecting metastases of ESCC. Cellular uptake of SG was significantly higher in TROP2-positive KYSE150 cells than in TROP2-negative EC109 cells. Both subcutaneous KYSE150 tumors and patient-derived xenograft models with high TROP2 expression demonstrated significantly higher accumulation of SG-IR800 compared to the control probe. Peritoneal metastases yielded an NIR signal in the second window (NIR-II) comparable to primary tumors, which outperformed the NIR-I signal. Metastatic lymph nodes showed higher NIR-II contrast than inflammatory nodes. This study demonstrates that the SG-IR800 probe possesses high specificity for TROP2-positive ESCC, facilitates the detection of metastatic lesions, and holds strong potential for guiding precise intraoperative navigation.