[99mTc(CO)3]-radiolabeled bevacizumab: In vitro and in vivo evaluation in a melanoma model

摘要

Introduction: 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 [99mTc(CO)3(OH2)3]+ and evaluate it in vivo and in vitro for melanoma imaging properties. Methods: Bevacizumab was radiolabeled with [99mTc(CO)3(OH 2)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 99mTc(CO)3-bevacizumab was stable. In vivo biodistribution studies revealed that tumor uptake of 99mTc(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 99mTc(CO) 3-bevacizumab in the tumor-bearing mice. This affinity was confirmed by immunoassays performed on B16F10 tumor samples. Conclusions: 99mTc(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.