Zr-89 immuno-PET targeting ectopic ATP synthase enables in-vivo imaging of tumor angiogenesis

Abstract

In this study, we synthesized a Zr-89-labeled anti-adenosine triphosphate synthase monoclonal antibody (ATPS mAb) for applications in immuno-positron emission tomography (PET) and evaluated its feasibility for angiogenesis imaging. The cellular uptake of Zr-89 ATPS mAb was measured after treatment of cancer cell lines in vitro, and its biodistribution was evaluated at 4, 24 and 48 h in vivo in mice bearing xenografts. PET images were acquired at 4, 24, 48, and 96 h after Zr-89 ATPS mAb administration. Tumor angiogenesis was analyzed using anti-CD31 immunofluorescence staining. The cellular uptake of Zr-89 ATPS mAb increased over time in MDA-MB-231 breast cancer cells but did not increase in PC3 prostate cancer cells. The tumor uptake of Zr-89 ATPS mAb at 24 h was 9.4 ± 0.9% ID/g for MDA-Mb-231 cells and was 3.8 ± 0.6% ID/g for PC3 cells (p = 0.004). Zr-89 ATPS mAb uptake in MDA-MB-231 xenografts was inhibited by the administration of cold ATPS mAb (4.4 ± 0.5% ID/g, p = 0.011). Zr-89 ATPS mAb uptake could be visualized by PET for up to 96 h in MDA-MB-231 tumors. In contrast, there was no distinct tumor uptake detected by PET in the PC3 xenograft model. CD31-positive tumor vessels were abundant in MDA-MB-231 tumors, whereas they were scarcely detected in PC3 tumors. In conclusion, ATPS mAb was successfully labeled with Zr-89, which could be used for immuno-PET imaging targeting tumor angiogenesis.