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Published on: May 11, 2014
Detection of Metastatic Lesions in Esophageal Cancer Using a TROP2 Antibody-Based Near-Infrared Probe
Huixiang Lan1, Danlin Ou1, Chaoming Mei2
1Department of Radiology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China.
Abstract:
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.
Insights
Sacituzumab govitecan (SG) labeled with IRDye800cw effectively detects TROP2-positive esophageal cancer metastases using near-infrared fluorescence imaging. This probe shows high specificity and potential for guiding intraoperative navigation during surgery.
Area of Science:
- Oncology
- Molecular Imaging
- Medical Diagnostics
Background:
- Sacituzumab govitecan (SG) is an antibody-drug conjugate targeting trophoblast cell surface antigen 2 (TROP2).
- Its utility in near-infrared (NIR) fluorescence imaging for detecting metastases remains largely uncharacterized.
- Esophageal squamous cell carcinoma (ESCC) frequently exhibits lymph node metastasis and TROP2 overexpression.
Purpose of the Study:
- To evaluate the efficacy of an IRDye800cw-labeled SG probe (SG-IR800) for detecting ESCC metastases.
- To assess the specificity and sensitivity of SG-IR800 in TROP2-expressing ESCC models.
Main Methods:
- Investigated cellular uptake of SG in TROP2-positive and TROP2-negative cell lines.
- Evaluated SG-IR800 accumulation in subcutaneous and patient-derived xenograft models of ESCC.
- Assessed NIR fluorescence imaging performance in the NIR-I and NIR-II windows for detecting peritoneal and lymph node metastases.
Main Results:
- Significantly higher cellular uptake of SG in TROP2-positive cells compared to TROP2-negative cells.
- Enhanced accumulation of SG-IR800 in TROP2-high tumors and patient-derived xenografts.
- NIR-II imaging detected peritoneal metastases and differentiated metastatic from inflammatory lymph nodes with high contrast.
Conclusions:
- The SG-IR800 probe exhibits high specificity for TROP2-positive ESCC.
- SG-IR800 facilitates the detection of metastatic lesions, including lymph nodes.
- This probe holds significant potential for precise intraoperative navigation in ESCC surgery.
