Modeling radioimmunotherapy with anti-CD20 antibody - optimal preload depending on lymphoma transcapillary solute exchange

Abstract

In radioimmunotherapy (RIT) preloading is a common strategy to improve biodistribution. The amount of unlabeled antibody is usually administered relative to the body surface area. However, studies have shown a considerably large interpatient variation of the biodistribution for the same preload. In this work, as a prerequisite for individualizing RIT, a physiologically based pharmacokinetic (PBPK) model for RIT using anti-CD20 antibody is developed and simulations are conducted based on physiological parameter values taken from the literature. The influence of different amounts of preloads for varying lymphoma transcapillary recirculation rates is determined. It is shown that - depending on the convection of antibody across the transvascular wall - an optimal preload amount does exist. For slow transport across the capillaries higher amounts of antibody as a preload are needed to sustain the flow into the interstitium (100 - 600 mg). For more rapid transport across the microvascular wall less unlabeled antibody is required (7.5 - 12 mg) to achieve the optimal lymphoma uptake. Thus, identifying the optimal dose for each patient or lymphoma, i.e., personalizing RIT, could considerably improve the biodistribution while saving antibody expenses.