Radioimmunotherapy with ¹³¹I-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 (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.
Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Saeb Ahmad
SA
Ashrafi
Seyed Jalal
SJ
Hosseinimehr
Kambiz
K
Varmira
Seyed Mohammad
SM
Abedi
D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000068258:Bevacizumab; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D051379:Mice; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000379:methods; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D061067:Antibodies, Monoclonal, Humanized; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab