Lu-177-DOTA- Bevacizumab: Radioimmunotherapy Agent for Melanoma

Abstract

Background: Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several types, including melanoma. Bevacizumab is a humanized monoclonal antibody directed against VEGF. Objective: To radiolabel Bevacizumab with 177-Lutetium as a potential radioimmunotherapy agent for melanoma. Methods: Bevacizumab was derivatized with DOTA-NHS-ester at 4 degrees C for 18 h. DOTA-Bevacizumab was radiolabeled with (LuCl3)-Lu-177 (15 MBq/mg) at 37 degrees C for 1 h. The studies were performed in healthy and B16F1 tumor-bearing C57BL/6J mice at 24 and 48 h (n = 5). Scinthigraphic imaging studies were performed at 24 h to determine the radiochemical stability, targeting specificity and pharmacokinetics of the 177Lutetium-labeled antibody. Results: DOTA-Bevacizumab was efficiently labeled with (LuCl3)-Lu-177 at 37 degrees C. The in-vitro stability of labeled product was optimal over 72 h. In-vivo biodistribution studies showed a high liver and tumor uptake of Lu-177-DOTA-Bevacizumab, with tumor-to-muscle ratios of 11.58 and 6.37 at 24 and 48 h p.i. Scintigraphic imaging of melanoma tumor-bearing C57BL/6J mice showed liver and a high tumor selective uptake of Lu-177-DOTA-Bevacizumab at 24 h. Conclusions: Our results support the potential role of Lu-177-DOTA-Bevacizumab as a novel radioimmunotherapy agent for melanoma. We hope that these novel molecular imaging agents will open the path to new diagnostic and therapeutic strategies for Melanoma disease.