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Published on: July 16, 2018
CD117-Targeted Intraoperative Imaging of Gastrointestinal Stromal Tumor Using a Stem-Cell-Factor-Labeled Fluorophore
Shinsuke Nomura1, Shinya Yokomizo2, Zhidong Wang3
1Gordon Center for Medical Imaging, Department of Radiology Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA, Department of Surgery, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan.
A novel near-infrared fluorescent nanoprobe targets CD117, improving gastrointestinal stromal tumor (GIST) visualization during surgery. This molecular imaging approach enhances GIST resection and aids in early diagnosis and prognosis.
Area of Science:
- Oncology
- Medical Imaging
- Nanotechnology
Background:
- Complete resection is the gold standard for nonmetastatic gastrointestinal stromal tumors (GIST).
- Accurate tumor localization during surgery is challenging due to GIST being covered by normal mucosal tissue.
- Suboptimal surgeries and increased cancer recurrence rates are linked to difficulties in GIST localization.
Purpose of the Study:
- To develop and evaluate a near-infrared (NIR) fluorescent nanoprobe for real-time GIST navigation.
- To specifically target CD117, a protein overexpressed in GIST, for enhanced surgical visualization.
- To assess the potential of CD117-targeted molecular imaging for intraoperative GIST management, early diagnosis, and prognosis monitoring.
Main Methods:
- Development of a nanoprobe by conjugating a zwitterionic NIR fluorophore (ZW800-1C) to a CD117 ligand (stem cell factor, SCF).
- In vitro evaluation of nanoprobe affinity for CD117-positive (GIST-T1) and CD117-negative (GIST-5 R) cell lines.
- In vivo assessment using a GIST-T1 xenograft mouse model and a spontaneous GIST mouse model (heterozygous Kit K641E mice).
Main Results:
- The nanoprobe demonstrated high affinity for CD117-positive GIST-T1 cells and no binding to CD117-negative cells.
- Strong and persistent NIR signals were observed in mice for over 72 hours post-injection.
- Successful detection of spontaneous GIST tumors in the cecum of heterozygous Kit K641E mice was achieved.
Conclusions:
- CD117-targeted molecular imaging using the developed NIR nanoprobe shows significant promise as an intraoperative strategy for GIST.
- This imaging approach can enhance surgical precision, potentially reducing recurrence rates.
- The nanoprobe holds potential for early GIST diagnosis and monitoring of patient prognosis before and after surgery.
