ABSTRACT
Development of effective antibody (Ab) therapy for cancer requires an understanding of Ab pharmacokinetics. Improved understanding of Ab pharmacokinetics will hopefully lead to improved strategy for cancer immunotherapy with radiolabeled Abs and other immunoconjugates. The realization that Ab interaction with the cell surface is predominantly irreversible, and cannot be adequately described by "functional affinity", should lead to more accurate pharmacokinetic models. From a theoretical perspective, it seems that it would generally be advantageous to use radiolabels that are retained within cells after Ab degradation, especially for cancer radioimmunotherapy, where a long duration of exposure is desired. It is well established that catabolism of conventionally iodinated proteins results in the generation, within lysosomes, of iodotyrosine, which rapidly leaves the cell. Limited invivo experiments with such radiolabels suggest that, in comparison with conventional iodination, higher tumor/nontumor ratios are obtained for certain normal tissues, while for other normal tissues the ratios are lower.
