Compartmental modelling of the uptake kinetics of the anti‐cancer agent topotecan in human breast cancer cells

Abstract A compartmental model for the in vitro uptake kinetics of the anti‐cancer agent topotecan is proposed. This model provides a description of the activity of the drug, and subsequent delivery of active form to the nuclear DNA target. The unknown model parameters are estimated from two‐photon laser‐scanning microscopy data, which provide concentrations of topotecan (active plus inactive forms) in the extracellular region containing live human breast tumour cells (MCF‐7 cell line), the cytoplasm and the nucleus. This determines an output structure for which the model is uniquely identifiable, that is, the unknown parameters are uniquely determined from noise‐free, continuous and perfect data. The model allows in silico predictions of the dose dependence of target binding. Copyright © 2005 John Wiley & Sons, Ltd.