title: Synthesis and evaluation of (99m)Tc chelate-conjugated bevacizumab.
abstract: Vascular endothelial growth factor (VEGF) is one of the classic factors involved in tumor-induced angiognesis in several solid tumors. Bevacizumab, a monoclonal antibody against VEGF, can be used as an imaging tool in preclinical studies. The aim of this study was to radiolabel Bevacizumab with (99m)Tc and to evaluate in vivo its imaging properties in an adenocarcinoma animal model. For this purpose, Bevacizumab was derivatized with Suc-HYNIC as a bifunctional coupling agent. A mixture of Tricine/SnCl(2).2H(2)O was added to Bevacizumab-HYNIC and radiolabeled with (99m)TcO(4)(-). The radiochemical stability of the radiolabeled antibody was assessed. Biodistribution and scintigraphy imaging were performed in normal CD1 female mice and in spontaneous adenocarcinoma tumor bearing CD1 mice (n = 5). We demonstrated that 99mTc-HYNIC-Bevacizumab was stable. In vivo biodistribution studies revealed that tumor uptake of (99m)Tc-HYNIC-Bevacizumab was 1.37 ± 0.51% and 5.33 ± 2.13% at 4 and 24 h postinjection, respectively. Scintigraphy image studies showed tumor selective uptake of (99m)Tc-HYNIC-Bevacizumab in the tumor-bearing mice. We conclude that (99m)Tc-HYNIC-Bevacizumb has the potential to be used as a tracer for tumor imaging in preclinical studies.
authors.affiliation: Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
authors.forename: Ximena
authors.initials: X
authors.lastname: Camacho
authors.forename: María Fernanda
authors.initials: MF
authors.lastname: García
authors.forename: Victoria
authors.initials: V
authors.lastname: Calzada
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fernández
authors.forename: Williams
authors.initials: W
authors.lastname: Porcal
authors.forename: Omar
authors.initials: O
authors.lastname: Alonso
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Gambini
authors.forename: Pablo
authors.initials: P
authors.lastname: Cabral
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging*; D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000378:metabolism / Q000493:pharmacokinetics*; D000068258:Bevacizumab; D016022:Case-Control Studies; D005240:Feasibility Studies; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging*; D051379:Mice; D011877:Radionuclide Imaging; D013667:Technetium / Q000378:metabolism / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D013667:Technetium