title: [(99m)Tc(CO)(3)]-radiolabeled bevacizumab: in vitro and in vivo evaluation in a melanoma model.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several tumor types, including melanoma. Bevacizumab, a monoclonal antibody against VEGF, could be used as an imaging tool in preclinical studies.
  
  
  OBJECTIVE
  To radiolabel bevacizumab with [(99m)Tc(CO)3(OH2)3](+) and evaluate it in vivo and in vitro for melanoma imaging properties.
  
  
  METHODS
  Bevacizumab was radiolabeled with [(99m)Tc(CO)3(OH2)3](+) ion in saline. The radiochemical stability of the labeled antibody was assessed. The biodistribution and scintigraphy imaging of the radiolabeled antibody were evaluated in normal C57BL/6J mice and in C57BL/6J mice bearing murine B16F1 melanoma tumors. Immunoreactivity of bevacizumab to murine tumors was determined from direct immunofluorescence and immunoblotting assays.
  
  
  RESULTS
  We demonstrate that (99m)Tc(CO)3-bevacizumab was stable. In vivo biodistribution studies revealed that tumor uptake of (99m)Tc(CO)3-bevacizumab was 2.64 and 2.51 %ID/g at 4 and 24 h postinjection. Scintigraphy image studies showed tumor selective uptake of (99m)Tc(CO)3-bevacizumab in the tumor-bearing mice. This affinity was confirmed by immunoassays performed on B16F10 tumor samples.
  
  
  CONCLUSIONS
  (99m)Tc(CO)3-bevacizumab could be used as an approach for tumor nuclear imaging in preclinical studies. This should be useful to provide insights into the angiogenic stimulus before and after chemotherapy, which might help improve current antitumor therapy.
authors: Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
authors: Ximena
authors: X
authors: Camacho
authors: María Fernanda
authors: MF
authors: García
authors: Victoria
authors: V
authors: Calzada
authors: Marcelo
authors: M
authors: Fernández
authors: Jose A
authors: JA
authors: Chabalgoity
authors: Maria
authors: M
authors: Moreno
authors: Rodrigo
authors: R
authors: Barbosa de Aguiar
authors: Omar
authors: O
authors: Alonso
authors: Juan Pablo
authors: JP
authors: Gambini
authors: Roger
authors: R
authors: Chammas
authors: Pablo
authors: P
authors: Cabral
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry / Q000276:immunology / Q000493:pharmacokinetics; D000068258:Bevacizumab; D007553:Isotope Labeling / Q000379:methods; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging*; D051379:Mice; D008810:Mice, Inbred C57BL; D015609:Organotechnetium Compounds; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013667:Technetium / Q000493:pharmacokinetics; D014018:Tissue Distribution; D059016:Tumor Microenvironment / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D042461:Vascular Endothelial Growth Factor A; C580820:technetium 99m tricarbonyl bevacizumab; D000068258:Bevacizumab; D013667:Technetium