Radioiodinated B6.2 monoclonal antibody: further characterization of a potential radiopharmaceutical for the identification of breast tumors.
A monoclonal antibody (B6.2) directed against human breast carcinomas and its F(ab')2 and Fab' fragments were labeled with 125I using Iodogen. Solid phase radioimmunoassay was used to evaluate the in vitro binding of the labeled antibodies to a human breast tumor metastasis to the liver, the MCF-7 breast tumor cell line and normal liver tissue. Scatchard analysis revealed that 125I-labeled B6.2 IgG and F(ab')2 bound to both breast tumors with affinity constants in the range 1.2-4.4 X 10(9) M-1, while the affinity constant for the binding of the 125I-labeled Fab' fragment to the metastasis and the MCF-7 line was 5.9 and 9.1 X 10(8) M-1, respectively. Serial blood sampling indicated that blood clearance of 125I activity decreased with increasing protein size. A comparison of tumor-to-tissue ratios at two doses of 125I-B6.2 IgG and F(ab')2 suggests that the optimal dose of antibody may depend on the imaging time. A comparison of the blood clearance of 125I activity following injection of 125I-B6.2 and nonspecific 125I-MOPC 21 demonstrated that the specific antibody cleared much more rapidly. When 125I-B6.2 was injected into mice bearing either breast or melanoma tumors, the thyroid uptake of 125I was significantly greater in mice with breast tumors. These results suggest that the catabolism of radiolabel from the specific antibody in the presence of tumor is greater and that this may be an important factor in determining the optimal radiolabel for immunoscintigraphy.
D000818:Animals; D000911:Antibodies, Monoclonal; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D002460:Cell Line; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D011865:Radioisotope Dilution Technique; D011877:Radionuclide Imaging; D013961:Thyroid Gland / Q000378:metabolism; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes