Radioimmunotherapy with super(131)I-Bevacizumab as a Specific Molecule for Cells with Overexpression of the Vascular Endothelial Growth Factor

Bevacizumab is a humanized monoclonal antibody that inhibits vascular endothelial growth factor A and is used for the treatment of several cancers. We labeled this monoclonal antibody with Iodine-131 ( super(131)I) and performed in vitro quality control and tumor cell growth inhibition tests. Bevacizumab was labeled with super(131)I using chloramine T. Radiochemical purity and stability in phosphate-buffered saline and human blood serum were determined using thin-layer chromatography and radio-sodium dodecyl sulfate-polyacrylamide gel elec-trophoresis, respectively, performed at different times. Cell-specific binding, internalization, and toxicity of the radiolabeled antibody were tested using the SKOV-3 ovarian cancer cell line. The biodishibution of super(131)I-bevacizumab was investigated using male mice. The radiochemical purity of the complex was 99% plus or minus 0.7%. Its stability in phosphate-buffered saline and human blood serum at 48 hours postpreparation was 78% plus or minus 1.2% and 93% plus or minus 0.6%, respectively. super(131)I-bevacizumab was significantly bound to SKOV-3. The internalization of super(131)I-bevacizumab was time dependent, and it was cleared from the blood after 24 hours. Significant reductions in SKOV-3 cell viability were achieved with super(131)I-bevacizumab at a concentration of 500 nM. A low accumulation of super(131)I-bevacizumab was observed in the stomach and salivary glands after 24 hours and 48 hours. These findings indicate that the new radiolabeled antibody should be further evaluated in animals and, possibly, in humans as a new radiopharmaceutical agent for use in radioimmunotherapy for ovarian cancer.