177Lu-labeled-VG76e monoclonal antibody in tumor angiogenesis: A comparative study using DOTA and DTPA chelating systems
Fani M., Bouziotis P., Harris AL., Psimadas D., Gourni E., Loudos G., Varvarigou AD., Maecke HR.
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.