99mTc-Labeled Bevacizumab via HYNIC for Imaging of Melanoma

 Vascular endothelial growth factor (VEGF) is one of the classic factors to tumour-induced angiogenesis in several types, including melanoma. Bevacizumab, a monoclonal antibody anti-VEGF, could be used as an imaging tool in clinical studies. The aim of this study was to radiolabeled Bevacizumab with 99mTc and evaluate it in vivoimaging properties. Bevacizumab was derivatized with the activated ester succinimidyl-hydrazinonicotinamide hydrochloride (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 sntibody was assessed. Biodistribution studies and SPECT-CT imaging were evaluated in healthy and tumor-bearing C57BL/6J mice at 1, 4 and 24 h (n =5). We demonstrated that 99mTc-HYNIC-Bevacizumab was stable over 24 h in solution and serum. In vivo biodistribution studies revealed tumor-to-muscle ratios of 99mTc-HYNIC-Bevacizumab was 9.28, 17.19 and 8.51 at 1, 4 and 24 h p.i. SPECT/CT imaging of tumor-bearing C57BL/6J mice showed tumor selective uptake of 99mTc-HYNIC-Bevacizumab. 99mTc-HYNIC-Bevacizumab could become a potential radiopharmaceutical to evaluate the expression of vascular endothelial growth factor (VEGF) in solid tumors and could be seen as a clinic tool for the screening of solid tumors that might respond to the Bevacizumab chemotherapy.