Evaluation of Novel Tumor-Targeted Near-Infrared Probe for Fluorescence-Guided Surgery of Cancer

Area of Science:

• Oncology
• Medical Imaging
• Nanotechnology

Background:

• Accurate cancer resection requires precise identification and removal of all malignant tissue.
• Fluorescent dyes are being developed to enhance tumor visualization during surgery.
• Targeting specific molecular markers on cancer cells can improve dye selectivity.

Purpose of the Study:

• To design, synthesize, and evaluate a novel folate receptor (FR)-targeted near-infrared (NIR) fluorescent dye (OTL38) for intraoperative tumor detection.
• To assess the dye's specificity, affinity, pharmacokinetics, and safety profile in preclinical and clinical settings.
• To determine the utility of OTL38 for fluorescence-guided cancer surgery.

Main Methods:

• Design and synthesis of OTL38, a NIR dye conjugated to a folate-targeting moiety.
• In vitro studies to determine binding affinity to FR-expressing cells.
• In vivo evaluation in murine tumor models and human cancer patients, assessing tumor uptake, biodistribution, and toxicity.
• Optical imaging to visualize malignant lesions.

Main Results:

• OTL38 demonstrated high affinity (approximately 1 nM) for FR-expressing cancer cells.
• The dye exhibited rapid clearance from non-target tissues (half-time <30 minutes).
• OTL38 enabled visualization of malignant lesions at non-toxic concentrations and provided excellent tumor contrast in both animal models and human patients.

Conclusions:

• OTL38 is a specific and effective FR-targeted NIR dye for cancer surgery.
• The dye's properties facilitate precise fluorescence-guided resection of malignant lesions.
• OTL38 shows significant promise as an imaging agent for improving surgical outcomes in cancer patients.