Purpose
Tumor-targeted positron emission tomography (PET) and fluorescence-guided surgery (FGS) could address current challenges in pre- and intraoperative imaging of gastric cancer. Adequate selection of molecular imaging targets remains crucial for successful tumor visualization. This study evaluated the potential of integrin αvβ6, carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule (EpCAM) and human epidermal growth factor receptor-2 (HER2) for molecular imaging of primary gastric cancer, as well as lymph node and distant metastases.

Methods
Expression of αvβ6, CEACAM5, EGFR, EpCAM and HER2 was determined using immunohistochemistry in human tissue specimens of primary gastric adenocarcinoma, healthy surrounding stomach, esophageal and duodenal tissue, tumor-positive and tumor-negative lymph nodes, and distant metastases, followed by quantification using the total immunostaining score (TIS).

Results
Positive biomarker expression in primary gastric tumors was observed in 86% for αvβ6, 72% for CEACAM5, 77% for EGFR, 93% for EpCAM and 71% for HER2. Tumor expression of CEACAM5, EGFR and EpCAM was higher compared to healthy stomach tissue expression, while this was not the case for αvβ6 and HER2. Tumor-positive lymph nodes could be distinguished from tumor-negative lymph nodes, with accuracy ranging from 82 to 93% between biomarkers. CEACAM5, EGFR and EpCAM were abundantly expressed on distant metastases, with expression in 88–95% of tissue specimens.

Conclusion
Our findings show that CEACAM5, EGFR and EpCAM are promising targets for molecular imaging of primary gastric cancer, as well as visualization of both lymph node and distant metastases. Further clinical evaluation of PET and FGS tracers targeting these antigens is warranted.@en