Immunochemical aspects of monoclonal antibodies important for radiopharmaceutical development.

Successful development of radiopharmaceuticals from monoclonal antibodies will require the control of several immunochemical aspects of the antibody molecules. A proposed set of methods is presented here for evaluating these immunochemical parameters. This approach consists of monitoring each monoclonal antibody harvest by selective affinity chromatography to determine the presence of detectable alterations in molecular homogeneity. The products are then evaluated by radioimmunoassay technique standardized for total immunoglobulin immunoreactivity. These assays are utilized to detect variation in the immunoreactivity secondary to changes in the hybridoma cell lines, and to measure any detectable denaturation secondary to purification, fragment production and radiolabeling. HPLC molecular sieving chromatography is presented as a practical and informative monitor of molecular stability of these radiopharmaceuticals in vitro and in vivo.