Fluorescence-guided cancer surgery using clinical available and innovative tumor-specific contrast agents

Abstract

Intraoperative NIRF imaging using ICG and MB was explored

in multiple important indications in cancersurgery. Imaging using ICG

resulted in accurate tumor imaging of liver metastases and SLN detection in

gastriccancer, with high TBRs and prolonged fluorescent signal. For these indications, our data suggests that fluorescence imaging should be implemented in the clinic. MB allowed successful imaging of parathyroid adenomas, neuro-endocrine tumors and breast cancer lesions, but accuracy and imaging characteristics can be improved by the introduction of more tumor-specifc contrastagents. However, in the meantime MB can be used for intraoperative guidance. Intraoperative imaging of ovarian cancer using the FRα specific EC17 and OTL38 showed highly specific and accurate tumor imaging with a high TBR and prolonged fluorescent signal in malignant lesions. Administration of these low molecular weight contrast agents resulted in rapid accumulation in tumor tissue and fast clearance from the rest of the body. Moreover, with the NIR fluorescent contrast agent OTL38 almost no background signal or auto uorescence was seen. Clinical translation using both healthy subjects and patients allowed a rapid determination of the optimal dose, formulation, and time-window for intraoperative imaging, facilitating fast clinical introduction of newly developed contrast agents in clinical trials