Unique Benefits of Tumor-Specific Nanobodies for Fluorescence Guided Surgery

Abstract

Tumor-specific fluorescence labeling is promising for real-time visualization of solid malignancies during surgery. There are a number of technologies to confer tumor-specific fluorescence. Antibodies have traditionally been used due to their versatility in modifications; however, their large size hampers efficient fluorophore delivery. Nanobodies are a novel class of molecules, derived from camelid heavy-chain only antibodies, that have shown promise for tumor-specific fluorescence labeling. Nanobodies are ten times smaller than standard antibodies, while maintaining antigen-binding capacity and have advantageous features, including rapidity of tumor labeling, that are reviewed in the present report. The present report reviews special considerations needed in developing nanobody probes, the status of current literature on the use of nanobody probes in fluorescence guided surgery, and potential challenges to be addressed for clinical translation.

Keywords: fluorescence-guided surgery; fluorescent nanobody; tumor-specific fluorescence.

Figure 1

Fluorescence signal is detectable at the tumor using an anti-CEA nanobody conjugated to IRDye800CW using clinically available FDA-cleared fluorescence imaging devices. Images were acquired after placing the animal within the minimally-invasive simulation dome (A) and switching between the bright light and the fluorescence mode (B). Representative images from fluorescence imaging using the Stryker Aim laparoscopic camera (Kalamazoo, MI, USA) and the corresponding bright light image (C,D). Tumors are approximately 7 mm–1 cm at the time of imaging.