Rhenium-186-mercaptoacetyltriglycine-labeled Monoclonal Antibody for Radioimmunotherapy:In vitroAssessment,in vivoKinetics and Dosimetry in Tumor-bearing Nude Mice

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Abstract
Stability and immunoreactivity of 186Re‐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 IgG1, A7, against a 45 kD glycoprotein in human colon cancer was radiolabeled with 186Re by using a chelating method with a mercaptoacetyltriglycine (MAG3). 186Re‐MAG3 complex was conjugated to A7 after esterification of 186Re‐MAG3 with tetrafluorophenol (TFP). The efficiency of 186Re‐MAG3‐TFP production and the labeling efficiency of A7 were 51–59% and 57–60%, respectively. Immunoreactivity of purified 186Re‐MAG3‐A7 was 68.2% at infinite antigen excess. In 0.9% NaCl at 4°C, the radioactivity (12.7 MBq/mg, 3.55 MBq/ml) dissociated with time from 186Re‐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°C could effectively prevent the radiolysis of 186Re‐MAG3‐A7 for 7 days. Immunoreactivity of 186Re‐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 186Re‐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 were superior to those of A7 labeled with radioiodine, affording greater therapeutic ratios than 131I‐A7. Because of the better image quality of 186Re‐MAG3‐A7 as well as more favorable dosimetry, 186Re‐MAG3‐A7 would be a better choice for RIT of colon cancer than 131I‐A7. These results indicated the feasibility of RIT with 186Re‐MAG3‐A7, though the prevention of radiolysis of the labeled antibody should be considered.