Plasmapheresis in radioimmunotherapy of micrometastases: a mathematical modeling and dosimetrical analysis

Abstract

The feasibility of combining plasmapheresis with a large administration of radiolabeled antibody in order to overcome the "binding-site" barrier to antibody penetration in targeting hematologically distributed micrometastases is examined. In such a strategy, intravenous administration of excess radiolabeled antibody, to saturate antigen sites on the cell cluster periphery, is followed by removal of unbound antibody from the plasma, by plasmapheresis, to reduce the absorbed dose to the red marrow. Plasma antibody kinetics are simulated by a non-linear compartmental model representing free and antigen-bound antibody. This provides the boundary condition for a model of antibody diffusion, saturable binding to and dissociation from antigen sites within a 200 microns diameter cluster of tumor cells. Using these models, the absorbed dose to the red marrow and the absorbed dose profile across the cell cluster are calculated. Changes in marrow and cell cluster absorbed dose from alterations in the onset time and rate of plasmapheresis are illustrated for antibody labeled with 123I, 125I and 131I. The results demonstrate that the "binding site" barrier may be overcome, yielding a 2- to 100-fold improvement in the cell cluster absorbed dose for a given bone marrow absorbed dose.