In vivo binding to tumor endothelium and erythrophagocytosis of intravenously administered RGD-erythrocytes in B16.F10 melanoma–bearing mice. (A) Immunohistologic detection of RGD-peptides in tumor tissue, 1 hour after intravenous administration, showing preferential accumulation in the tumor rim. Scale bar represents 200 μm. (B) Fluorescence microscopy image of a tumor blood vessel showing specific binding of RGD-erythrocytes to the vessel wall, 4 hours after intravenous administration of RGD-coupled DiD-labeled erythrocytes. Scale bar represents 30 μm. (C) Fluorescence microscopy image of a tumor blood vessel showing circulating plain DiD-labeled erythrocytes at 4 hours after intravenous administration. Scale bar represents 50 μm. (D) Light microscopy image of a tumor blood vessel showing internalization of multiple erythrocytes by endothelial cells (indicated by arrow) 2 hours after injection. Scale bar represents 10 μm. (E) Transmission electron microscopy image of an erythrocyte phagocytosed by a tumor endothelial cell (indicated by arrow) 4 hours after administration. Scale bar represents 2 μm.