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
Methods: Bevacizumab was derivatized with DOTA-NHS-ester at 4 ºC for 18 h. DOTABevacizumab
was radiolabeled with 177LuCl3 (15 MBq/mg) at 37 ºC 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 177LuCl3 at 37 °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 177Lu-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 177Lu-DOTA-Bevacizumab at 24 h.
Conclusions: Our results support the potential role of 177Lu-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.