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

Abstract

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 (¹³¹I) and performed in vitro quality control and tumor cell growth inhibition tests. Bevacizumab was labeled with ¹³¹I 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 electrophoresis, 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 biodistribution of ¹³¹I-bevacizumab was investigated using male mice. The radiochemical purity of the complex was 99% ± 0.7%. Its stability in phosphate-buffered saline and human blood serum at 48 hours postpreparation was 78% ± 1.2% and 93% ± 0.6%, respectively. (131)I-bevacizumab was significantly bound to SKOV-3. The internalization of ¹³¹I-bevacizumab was time dependent, and it was cleared from the blood after 24 hours. Significant reductions in SKOV-3 cell viability were achieved with (131)I-bevacizumab at a concentration of 500 nM. A low accumulation of ¹³¹I-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.

Resveratrol Sensitizes Selectively Thyroid Cancer Cell to 131-Iodine Toxicity

“…Untreated and treated thyroid cancer and HFFF2 cells were subjected to cell proliferation assay using MTT to quantify the metabolic activity to cleave tetrazolium salts [25, 26]. Cells (20,000) were seeded in 96-well plates.…”

Radiosensitive effect of curcumin on thyroid cancer cell death induced by radioiodine-131

“…The MTT test is based on the strength of mitochondrial enzymes to decrease MTT (pale yellow) to formazan crystals (dark blue). Owing to their impenetrability through the cell membrane, formazan crystals collect in cells (Ashrafi et al , 2012 ). Cells (20,000) were seeded in 96-well plates.…”

Therapeutic Efficacy of Alpha-RIT Using a 213Bi-Anti-hCD138 Antibody in a Mouse Model of Ovarian Peritoneal Carcinomatosis

“…The second study showed higher CD138 expression in all cancer types compared to healthy ovarian tissue, without any correlation in terms of chemoresistance or exposure to estrogens ( 11 ). Therefore, we considered CD138 as a potential innovative target antigen for the treatment of ovarian cancer by RIT, in the same way as other emerging targets such as Her2 ( 29 ) or VEGF ( 30 ). This choice was strengthened by the results that we obtained in this study on CD138 expression and RIT.…”