Monoclonal antibodies or other ligands are potentially useful for the diagnosis and treatment of tumors. Their therapeutic and diagnostic potential depends on the ability of the antibody to reach the target cell. We have developed a theoretical model for the biodistribution of whole monoclonal antibody and the FAB2prime and FABprime fragments into the lymphatic and capillary systems following intravenous and subcutaneous injection. The model incorporates processes for transcapillary and translymphatic solvent and solute movement that account for a) hydrostatic and osmotic pressure differences between the injected solution and fluid surrounding the injection site, b) differences in the available pore area for transport into the lymphatic and capillary systems and c) specific and nonspecific binding of antibody molecules to tissue cells at the injections site. The partial differential equations describing the model are being solved numerically on a VAX/11-780 computer. Significant theoretical findings to date include the following: 1) most of the antibody that leaves the injection site to enter the lymphatics does so by convection in the fluid also entering the lymphatics, 2) most of the water leaving the injection site does so by entering the capillary system 3) intravenously administered antibody rapidly leaves the blood to enter major visceral organs and to a lesser extent skeletal muscle, skin and bone; 4) monoclonal antibody with specific target antigens in major organs receives greater than 75 percent of the administered dose; 5) the FAB fragment, when administered intravenously, demonstrates a much greater uptake relative to a nonspecific antibody over the whole antibody or over the FAB2prime fragment. The concepts arising from this study are directly applicable to the design of clinical studies with monoclonal antibodies and other ligands.
