Endothelium capture‐based liver segment imaging using vascular endothelial growth factor receptor 2 in preclinical ex vivo models

Abstract

Background Near‐infrared (NIR) imaging of liver segments provides substantial information for surgeons performing liver resection. It was hypothesized that ramucirumab, an endothelium‐specific antibody approved by the Food and Drug Administration, could be used for liver segment imaging using the endothelium capture principle. Methods The capture efficacy of anti‐vascular endothelial growth factor receptor (VEGFR) 2 monoclonal antibodies (mAbs) and segment imaging were studied in a mouse model. Binding of ramucirumab in human and porcine tissues was studied using immunofluorescence staining. Isolated porcine liver perfusion was used to analyse the labelling and NIR imaging of selected liver segments. Results VEGFR2 is well expressed on the endothelium of the smallest microvascular blood vessels in mouse, porcine and human liver tissues, as well as in human liver tumours. Perfusion of selected segments in the isolated liver model showed high capture of the anti‐VEGFR2 (clone 522302) mAb and ramucirumab in mice and pigs respectively. NIR imaging of selected segments was achieved using isolated porcine liver perfusion with IRDye® 800CW‐conjugated ramucirumab. Conclusion VEGFR2 is well expressed on the smallest microvascular blood vessels and can capture antibodies during single intravascular passages with high efficacy. The ex vivo imaging of a selected segment using endothelial capture of ramucirumab demonstrates the potential of this antibody for intraoperative navigation in liver surgery. Surgical relevance Imaging of liver segments provides substantial information for surgeons when performing liver resection. The antivascular endothelial growth factor receptor (VEGFR) 2 antibody ramucirumab conjugated with near‐infrared dye could visualize selected liver segments using an endothelial capture‐based approach in an isolated perfusion liver model. The ex vivo imaging of a selected segment using endothelial capture of ramucirumab demonstrates the potential of this anti‐VEGFR2 antibody for intraoperative navigation in liver surgery.