In vitro validation of permeability-surface area product derived by distributed parameter model with DCE-MRI

Introduction: Dynamic contrast enhanced MRI (DCE-MRI) with tracer kinetic modeling has been proposed as a biomarker of tumor angiogenesis assessment in humans. Several tracer kinetic models, distributed parameter model (DP), St. Lawrence and Lee model (ATH), and conventional compartmental model (CC), have been proposed to calculate permeability-surface area product (PS). It was found that PS correlated with drug exposure and might predict patient outcome in an anti-angiogenic drug clinical trial. Recently, hollow fiber bioreactors (HFB) has been used to distinguish extravasation rates of paramagnetic CA of different molecular weights by DCE-MRI. HFB, typically used for cell culture, mimicks well the human capillary system and thus is ideal to be used to validate the microcirculatory parameters obtained by tracer kinetic modeling. The aim of this study is to validate the permeability-surface area product obtained by the DP model in a HFB.