In vivo tumor targeting imaging of cyclic RGD-modified heparin derivative to avb3-integrin expressing tumor

Therapeutic target for over-expressed avb3 integrins in angiogenic endothelial cells and tumors is one of the promising approaches for cancer imaging and therapy. In the previous study, we demonstrated that heparin–lithocholic acid functionalized with cyclic RGDyK (cRGD–HL) had potent angiogenesis inhibition and tumor regression effects. The aim of this study is to validate the targeting property and specificity of cRGD–HL to avb3 integrin-expressing endothelial cells and tumor tissues by Cy5.5-labeled cRGDyK (RGD-Cy5.5) as avb3 integrin imaging agent and near-infrared fluorescence (NIRF) imaging systems. In this study,we demonstrated that cRGD–HL markedly inhibited the binding of fluorescein-labeled avb3 antibody to avb3 integrin-expressing endothelial cells when compared to nonfunctionalized heparin derivatives. Furthermore, in vivo NIRF images showed that cRGD–HL could decrease the NIRF signal intensities in both avb3 integrin-positive tumor (U87 MG) and avb3 integrin-negative tumor (SCC7) more effectively than non-functionalized heparin derivatives could. Therefore, with the help of avb3 integrin imaging agent and NIRF imaging systems, we verified that the functionalized cRGD–HL has much stronger tumor targeting property and specificity against avb3 integrin-expressing endothelial cells and tumors than non-functionalized heparin derivatives. Also,we believe that cRGD–HL will be useful and give affirmative outcomes for the treatment of angiogenesis-related diseases.