Synthesis and Evaluation of 99mTc Chelate-conjugated Bevacizumab

Ximena      Camacho; Maria      Fernanda Garcia; Victoria      Calzada; Marcelo      Fernandez; Williams      Porcal; Omar      Alonso; Juan      Pablo Gambini; Pablo      Cabral

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 99mTc 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/SnCl2.2H2O was added to Bevacizumab-HYNIC and radiolabeled with 99mTcO4 -. 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 99mTc- 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 99mTc-HYNIC-Bevacizumab in the tumor-bearing mice. We conclude that 99mTc-HYNIC-Bevacizumb has the potential to be used as a tracer for tumor imaging in preclinical studies.

Keywords: Radiolabeling Bevacizumab, HYNIC, 99mTc, VEGF, Preclinical imaging

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