CD117-Targeted Intraoperative Imaging of Gastrointestinal Stromal Tumor Using a Stem-Cell-Factor-Labeled Fluorophore

Abstract

Complete resection without damaging the capsule is the gold-standard surgical approach for nonmetastatic gastrointestinal stromal tumors (GIST). However, accurately locating tumors during surgery is challenging because GIST is covered by normal mucosal tissue, leading to suboptimal surgeries and increased cancer recurrence rates. To enhance surgical care for GIST, a cutting-edge near-infrared (NIR) fluorescent nanoprobe is presented that enables real-time navigation of GIST by specifically targeting CD117, a protein frequently overexpressed in GIST. By attaching a zwitterionic NIR fluorophore called ZW800-1C to a CD117 ligand, stem cell factor (SCF), precise targeting is achieved while minimizing nonspecific tissue interactions. In in vitro studies, the high affinity of nanoprobe for CD117-positive GIST-T1 cell lines is demonstrated, while exhibiting no binding to CD117-negative cells or GIST-5 R cells. In a xenograft model of GIST-T1 in mice, the nanoprobe produces strong and persistent NIR signals that last over 72 h following a single intravenous injection. Moreover, the nanoprobe successfully detects spontaneous tumors in the cecum of heterozygous Kit K641E mice. In these findings, the promise of CD117-targeted molecular imaging is highlighted as an intraoperative strategy for GIST. Furthermore, this imaging approach holds potential for early diagnosis, as well as monitoring GIST prognosis before and after surgical resection.