EWS–FLI1‐targeting peptide identifies Ewing sarcoma tumor boundaries and lymph node metastasis via near‐infrared imaging

Ewing sarcoma (ES) is one of the most aggressive types of pediatric tumors. The lack of tools for the identification of ES has largely hindered clinical diagnosis and the improvement of treatment. To address this challenge, we synthesized a near‐infrared (NIR) fluorescent probe (CS2‐N‐E9R) that targets the ES‐specific fusion protein EWS–FLI1 (E/F). This probe exhibited specific and high binding affinity to E/F. Further studies in animal models showed that CS2‐N‐E9R can be used to identify the boundaries of ES and lymph node metastases under a complex biological environment. These results demonstrate that CS2‐N‐E9R is a promising probe for early diagnosis and surgical guidance of ES through molecularly targeted NIR imaging.