Direct radiolabeling of monoclonal antibodies with generator-produced rhenium-188 for radioimmunotherapy: labeling and animal biodistribution studies.
The use of 188Re from an alumina-based 188W/188Re generator has been investigated for antibody radiolabeling. It was found that, with simple labeling techniques, 188Re can be used immediately after elution. The direct radiolabeling of intact antibodies with 188Re is described. Lyophilized antibody preparations have been reconstituted with 188Re taken directly from the generator at specific activities of up to 15 mCi of 188Re per mg of antibody. Radiolabeling yields of 90 to 98% have been obtained, with the incorporation rate being dependent upon time and the relative concentrations of the reagents. It was determined that the conjugates were immunoreactive and stable when challenged by serum in vitro, with 188Re-immunoglobulin G showing adequate resistance to reoxidation with no transfer of 188Re to serum protein. 188Re-antibody conjugates were shown to clear from the blood faster than the corresponding 131I-labeled antibody, giving rise to good tumor/nontumor ratios at 24 to 72 h postinjection, while serum samples taken from the animals have shown that the circulating 188Re remained bound to immunoglobulin G. The combination of the technologies of the 188W/188Re generator, the direct labeling methodology, and the use of single-vial lyophilized antibody makes the use of 188Re-radiolabeled monoclonal antibodies a simple and convenient method of cancer radioimmunotherapy with a beta-emitting radionuclide.[1]References
- Direct radiolabeling of monoclonal antibodies with generator-produced rhenium-188 for radioimmunotherapy: labeling and animal biodistribution studies. Griffiths, G.L., Goldenberg, D.M., Knapp, F.F., Callahan, A.P., Chang, C.H., Hansen, H.J. Cancer Res. (1991) [Pubmed]
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