A model system that predicts effective half-life for radiolabeled antibody therapy

Abstract

Radiolabeled antibodies to tumor associated proteins localize in both experimental and clinical cancers. In the therapeutic applications of radiolabeled antibody, tumor effective half-life (composite of biological and physical half-lives), along with the concentration of isotope deposited and energies of the isotope used, determine the tumor dose. Antibodies directed against the same antigenic specificity but derived from different species have varied tumor and whole body effective half-lives and as a result, achieve different tumor doses. In vitro testing does not evaluate the in vivo differences in effective half-life that affect tumor dose. We have developed an animal model to evaluate the effective half-life and biodistribution of radiolabeled immunoglobulin (IgG) from diverse species. To determine the relevance of such a model, the effective half-lives and tissue distributions of the different immunoglobulins in the model were compared to those obtained from the clinical program using the same radiolabeled antibody preparations. In both the experimental model and in the clinical trials, radiolabeled immunospecific and normal IgG derived from monkey, rabbit, and porcine sources had the longest effective half-lives, goat and sheep had intermediate effective half-lives, and chicken and turkey had the shortest effective half-lives. Prescreening of bovine and baboon normal IgG predict long half-lives and similar organ distributions. These species have been immunized for clinical use. Bovine IgG has a long clinical half-life and has been added to our other successful antibodies. Baboon IgG is now ready for clinical testing. The value of this model system is that it appears to be an effective in vivo preclinical screen for tumor effective half-life of antibodies and IgG from diverse species, thus guiding potential clinical use.