Multimodality PET and Near-Infrared Fluorescence Intraoperative Imaging of CEA-Positive Colorectal Cancer

Area of Science:

• Oncology
• Medical Imaging
• Bioconjugation Chemistry

Background:

• Molecular imaging is crucial for cancer diagnosis, staging, therapy targeting, and response monitoring.
• Multimodality imaging enhances tumor localization, improving surgical precision.
• Developing a single agent for real-time positron emission tomography (PET) and fluorescence-guided surgery (FGS) is a key goal for next-generation cancer care.

Purpose of the Study:

• To develop and evaluate a novel dual-labeled antibody conjugate for multimodality molecular imaging.
• To assess the agent's utility in simultaneous near-infrared (NIR) fluorescence imaging and PET/MRI for cancer detection and surgical guidance.

Main Methods:

• A humanized anti-CEA antibody (M5A-IR800) was conjugated with a NIR 800 nm dye and a metal chelate (DFO) for zirconium-89 (89Zr) labeling.
• The dual-labeled 89Zr-DFO-M5A-SW-IR800 conjugate was tested in a human colorectal cancer xenograft mouse model.
• Evaluations included NIR fluorescence imaging, serial PET/MRI scans (24, 48, 72 hours), biodistribution, and blood clearance.

Main Results:

• NIR fluorescence imaging demonstrated high tumor targeting with minimal liver uptake.
• PET/MRI imaging revealed persistent tumor localization from 24 hours onwards.
• PET scans showed higher liver activity than tumor, contrasting with NIR imaging, highlighting modality-specific differences in sensitivity and penetration depth.

Conclusions:

• The pegylated anti-CEA M5A-IR800-Sidewinder conjugate shows significant potential for multimodality imaging.
• This agent can facilitate intraoperative fluorescence-guided surgery by combining NIR fluorescence and PET/MR capabilities.
• The study validates a promising tool for enhanced surgical management of cancer.