Dual-Labeled anti-CEA antibody for Near-Infrared Fluorescence and PET Imaging of Colorectal Cancer.

Background/purpose. Multi-modality imaging is a major diagnostic component for cancer management, enabling detection, staging of disease, targeting therapy, and monitoring the therapeutic response. The development of a single agent for real-time non-invasive immunoPET imaging and fluorescence guided surgery (FGS) will provide the next generation tool in the surgical management of cancer. Methods. The humanized anti-CEA M5A-IR800 "sidewinder" (M5A-IR800-SW) antibody-dye conjugate has a NIR 800nm dye incorporated into a PEGylated linker and conjugated with the metal chelate p-SCN-Bn-deferoxamine (DFO) for zirconium-89 (Zr-89, half-life 78.4 h) PET imaging. The dual-labeled Zr-89-DFO-M5A-SW-IR800 was evaluated for NIR fluorescence imaging, PET/MRI imaging, terminal tissue biodistribution and blood clearance in a human colorectal cancer LS174T xenograft mouse model. Results. The Zr-89-DFO-M5A-SW-IR800 NIR fluorescence imaging showed high tumor and liver localization that was confirmed by PET imaging. Serial PET/MRI imaging was performed at 24 h, 48 h and 72 h and showed tumor localization visible at 24 h that persisted throughout the experiment. However, the PET scans showed higher activity for the liver than the tumor, compared to the NIR fluorescence imaging. This difference is an important finding as it quantifies the expected difference due to the sensitivity and depth of penetration between the 2 modalities.