Fluorescence-guided surgery using tumor-targeted imaging agents has emerged over the past decade as a promising and effective method of intraoperative cancer detection. A large number of fluorescently labelled molecules related to the hallmarks of cancer have been developed to illuminate target lesions. New approaches are being implemented to translate these tumor-targeting imaging agents into the clinic, although only a few have made it past early-phase clinical trials. For this translational process to succeed, these imaging agents and their related camera systems have to operate in close harmony to enable real-time intraoperative visualization.

Indocyanine green (ICG) has been used as a contrast agent for intraoperative detection of diverse tumor types, which is based on two characteristics of ICG: hepatic clearance and the enhanced permeability and retention (EPR) effect. Solid tumors (other than hepatobiliary tract) could be visualized by the EPR effect, which is based on the visualization with ICG of the increased permeability and reduced drainage in tumor tissue after tumor-induced angiogenesis, albeit with limited tumor-to-background ratio. Intravenous injection is recommended for good intraoperative visibility of liver tumors, adrenal tumors and peritoneal metastases. Intraoperative injection is optimal for detection of peritoneal metastases and adrenal tumors, although for detection of liver tumors it is preferable to inject ICG 24 h before surgery.

Sentinel lymph node (SLN) mapping is standard of care in several tumor types, for instance for melanoma and breast cancer. The identification of the SLN, or first draining lymph node from the tumor, is often performed using peritumoral injection of blue dye and/or Technetium-99m (Tc-99m), which both have certain disadvantages. Blue dye has no penetration capacity and a gamma probe does not allow visual identification. Today, NIR fluorescence imaging of SLNs with indocyanine green (ICG) as a new and additional modality is frequently being used for SLN mapping in malignancies of the oesophagus, stomach, colon, bladder, prostate, head and neck, cervix, endometrium, and ovarium.