title: 177Lu-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 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.
authors.affiliation: Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400 Montevideo. Uruguay.
authors.forename: Ximena
authors.initials: X
authors.lastname: Camacho
authors.affiliation: Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400 Montevideo. Uruguay.
authors.forename: Victoria
authors.initials: V
authors.lastname: Calzada
authors.affiliation: Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400 Montevideo. Uruguay.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fernandez
authors.affiliation: Centro de Medicina Nuclear, Hospital de Clínicas . Uruguay.
authors.forename: Omar
authors.initials: O
authors.lastname: Alonso
authors.affiliation: Laboratório de Oncologia Experimental, Faculdade de Medicina, Universidade de Sao Paulo, Av. Dr. Arnaldo Nº 455- Cerqueira Cesar - CEP: 01246903 , Sao Paulo, Brazil.
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
authors.affiliation: Clínica Hematológica. Hospital de Clínicas. Facultad de Medicina. Universidad de la Republica, Montevideo. Uruguay.
authors.forename: Eloisa
authors.initials: E
authors.lastname: Riva
authors.affiliation: Centro de Medicina Nuclear, Hospital de Clínicas . Uruguay.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Gambini
authors.affiliation: Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, 11400 Montevideo. Uruguay.
authors.forename: Pablo
authors.initials: P
authors.lastname: Cabral
mesh_terms: D000818:Animals; D000068258:Bevacizumab / Q000494:pharmacology*; D008187:Lutetium / Q000494:pharmacology*; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D016499:Radioimmunotherapy / Q000379:methods*; D011868:Radioisotopes / Q000494:pharmacology*; D011877:Radionuclide Imaging; D013388:Succinimides / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: C502492:DOTA-NHS; D011868:Radioisotopes; D013388:Succinimides; D000068258:Bevacizumab; D008187:Lutetium; C000615061:Lutetium-177
keywords: 177Lu; Bevacizumab; DOTA; VEGF; melanoma; radioimmunotherapy agent