Transport of fluid and macromolecules in tumors. III. Role of binding and metabolism.

摘要: Abstract We have previously developed a general theoretical framework for transvascular exchange and extravascular transport of fluid macromolecules in tumors. The model was first applied to homogeneous, alymphatic tumor, with no binding ( Baxter Jain, 1989 ). For nonbinding molecules the interstitial pressure found be major contributing factor heterogeneous distribution within solid A steep gradient predicted at periphery verified recent experiments. second paper this series looked role perfusion lymphatics on concentration profiles 1990 present work presents specific metabolism macromolecular uptake distribution. In investigation IgG its fragment, Fab, were modeled convective-diffusion equation which includes as well exchange. effects molecular weight, affinity, antigen density, initial dose, plasma clearance, vascular permeability, metabolism, necrosis considered. An expression optimal affinity derived. main conclusion is that an antibody highest possible should used except when: (i) there are significant necrotic regions; (ii) diffusive permeability very small; (iii) uniform required microscopic scale. concentrations achieved by continuous infusion, but specificity ratio bolus injections. Antibody reduces both total ratio, especially later times. addition, amount material sequestered core. Our compared three previous models literature. Unlike models, combines nonuniform filtration, binding, determine macroscopic profiles. addition supporting conclusions, our offers some new strategies therapy.