Rhenium-186-mercaptoacetyltriglycine-labeled monoclonal antibody for radioimmunotherapy:: In vitro assessment, in vivo kinetics and dosimetry in tumor-bearing nude mice

Stability and immunoreactivity of Re-186-labeled monoclonal antibody were examined, and its in vivo kinetics was investigated in tumor-bearing Balb/c nu/nu female mice to assess the feasibility of using it in radioimmunotherapy (RIT), A murine IgG(1), A7, against a 45 kD glycoprotein in human colon cancer was radiolabeled with Re-186 by using a chelating method with a mercaptoacetyltriglycine (MAG3). Re-186-MAG3 complex was conjugated to A7 after esterification of Re-186-MAG3 with tetrafluorophenol (TFP), The efficiency of Re-186-MAG3-TFP production and the labeling efficiency of A7 were 51-59% and 57-60%, respectively, Immunoreactivity of purified Re-186-MAG3-A7 was 68.2% at infinite antigen excess, In 0.9% NaCl at 4 degrees C, the radioactivity (12.7 MBq/mg, 3.55 MBq/ml) dissociated with time from Re-186-MAG3-A7 as a small molecular weight moiety because of autoradiolysis. The addition of ascorbic acid, 5 mg/ml, as a radioprotectant or storage at -80 degrees C could effectively prevent the radiolysis of Re-186-MAG3-A7 for 7 days, Immunoreactivity of Re-186-MAG3-A7, 6.70 MBq/mg (6.66 MBq/ml), stored in the presence of ascorbic acid was well retained up to 8 days after the preparation, In colon cancer xenografted mice, 31.0% of the injected dose/g of Re-186-MAG3-A7 had accumulated in the tumors at 24 h postinjection, Estimated radiation dose to tumors was 14.9 cGy/37 kBq up to 8 days postinjection which was 12-fold greater than the whole-body radiation dose. These in vivo characteristics mere superior to those of A7 labeled with radioiodine, affording greater therapeutic ratios than I-131-A7, Because of the better image quality of Re-186-MAG3-A7 as well as more favorable dosimetry, Re-186-MAG3-A7 would be a better choice for RIT of colon cancer than I-131-A7. These results indicated the feasibility of RIT with Re-186-MAG3-A7, though the prevention of radiolysis of the labeled antibody should be considered.