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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 (186)Re‐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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
1998
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921918/ https://www.ncbi.nlm.nih.gov/pubmed/9765625 http://dx.doi.org/10.1111/j.1349-7006.1998.tb00642.x |
Sumario: | Stability and immunoreactivity of (186)Re‐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 (186)Re by using a chelating method with a mercaptoacetyltriglycine (MAG3). (186)Re‐MAG3 complex was conjugated to A7 after esterification of (186)Re‐MAG3 with tetrafluorophenol (TFP). The efficiency of (186)Re‐MAG3‐TFP production and the labeling efficiency of A7 were 51–59% and 57–60%, respectively. Immunoreactivity of purified (186)Re‐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 (186)Re‐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 (186)Re‐MAG3‐A7 for 7 days. Immunoreactivity of (186)Re‐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 (186)Re‐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 (131)I‐A7. Because of the better image quality of (186)Re‐MAG3‐A7 as well as more favorable dosimetry, (186)Re‐MAG3‐A7 would be a better choice for RIT of colon cancer than (131)I‐A7. These results indicated the feasibility of RIT with (186)Re‐MAG3‐A7, though the prevention of radiolysis of the labeled antibody should be considered. |
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