SIMULATION OF TUMOR-SPECIFIC DELIVERY OF RADIOLIGAND COMPARISON OF ONE-STEP, 2-STEP, AND GENETIC TRANSDUCTION SYSTEMS

A mathematical model simulation was performed to estimate the amount o f radioactivity in plasma, normal tissues, and tumor tissue through th ree delivery approaches: one step radiolabeled monoclonal antibody (MA b) CC49 i.v. bolus injection, two step method with biotin conjugated C C49 i.v. bolus injection followed 72 hours later by i.v. bolus radiola beled streptavidin injection, and gene therapy method to express bioti n on the tumor cell surface followed by i.v. bolus radiolabeled strept avidin injection. The mathematical model was built based on a system o f ordinary differential equations consisting of inputs and outputs of model components in plasma, normal tissues, and tumor tissue. Through computer modeling, we calculated concentrations of each component for plasma, tumor and normal tissues at various time points. Radioactivity ratios of tumor to plasma and tumor to normal tissues increased with time. The increase of tumor to normal tissue ratios was much faster fo r the gene therapy approach than for single step and two step approach es, e.g., a ratio of 24.26 vs. 2.06 and 6.24 at 72 hours after radioli gand injection. Radioactivity ratios predicted by the model varied wit h the amount of radioactivity injected and the time interval between i njections. The model could be used to evaluate different radioimmunoth erapy strategies and to predict radioactivity biodistribution using ot her receptor-ligand systems.