¹⁷⁷Lu-labeled-VG76e monoclonal antibody in tumor angiogenesis: A comparative study using DOTA and DTPA chelating systems

Vascular Endothelial Growth Factor (VEGF) is one of the molecules which regulate angiogenesis, a phenomenon observed in many diseases, including cancer. VG76e, an anti-VEGF monoclonal antibody, was labeled with 177Lu via p-SCN-Bz-DOTA and CHX-A″-DTPA chelating systems, in order to investigate its possible therapeutic use. Labeling was performed by a 30 min incubation of 177LuCl3 and each immunoconjugate, at 37°C. Radiochemical analysis showed the formation of a single radioactive species, at a yield higher than 98%, for both immunoconjugates. Kits have been formulated for both VG76e-DOTA and VG76e-DTPA. Stability studies, in the presence of a competitor excess, showed that both radiolabeled species remained sufficiently stable (95%) for at least 48 h. Biodistribution results in normal mice were similar for both radioimmunoconjugates, with no significant bone uptake. Gamma camera images of tumor-bearing mice showed satisfactory visualization of the tumor 24 h p.i., while a higher uptake was observed at 48 h p.i. Our findings indicate that both the bifunctional chelating agents p-SCN-Bz-DOTA and CHX-A″-DTPA can be used for the labeling of VG76e with 177Lu, with high labeling yield and stability. Their in vivo behaviour in normal and tumor-bearing mice looks promising and they can be successfully used for tumor imaging studies. © by Oldenbourg Wissenschaftsverlag.