Abstract
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Objectives Kaposi's sarcoma (KS) is a highly vascularized tumor that is associated with human herpesvirus (HHV)-8. Recently, therapies focusing on EphrinB2, and its binding target EphB4, have become potentially important considerations in KS treatment strategies. In this research, we developed EphB4/EprhinB2 specific PET probes to quantify EphB4/EphrinB2 expression non-invasively and repetitively in KS xenografts.
Methods Anti-EphB4/EphrinB2 antibody was conjugated with the macrocyclic chelating agent DOTA and labeled with 64Cu. The binding affinity of the resulting probes was confirmed through a binding assay with immobilized EphB4/EphrinB2 protein. The microPET imaging was investigated in a KS-SLK xenograft model.
Results 64Cu labeled Anti-EphB4/EphrinB2 antibodies were obtained in reasonable yield, and the target binding ability was confirmed through in vitro assay. In our pilot in vivo studies, the KS-SLK tumors were clearly visualized with high tumor-to-background contrast. The prominent tumor uptake could be attributed to the high EphrinB2 expression in KS tumor cells. Although the tumor KS-SLK cells did not overexpress EphB4, it may be present in the tumor vasculature, where it interacts with EphrinB2 and promotes angiogenesis. 64Cu labeled DOTA-anti-EphB4 antibody was also imaged in this KS-SLK tumor model. The tumor could be clearly visualized in microPET images. The tumor accumulation increased overtime with the 72 h time point showing the highest tumor uptake.
Conclusions We have demonstrated the feasibility of imaging KS with Cu labeled anti-EphB4/anti-EphrinB2 antibodies. The success of this approach could help us evaluate disease course and therapeutic efficacy at the earliest stages of anti-EphrinB2 treatment. Moreover, these newly developed PET probes could have important applications in other cancer types overexpressing EphB4 or EphrinB2, such as breast cancer and melanoma.
Research Support This research was supported by the Margaret E. Early Medical research fund