Mathematical Model for Evaluation of Tumor Response in Targeted Radionuclide Therapy with 211At Using Implanted Mouse Tumor.

Abstract

Recent introduction of alpha-emitting radionuclides in targeted radionuclide therapy has stimulated the development of new radiopharmaceuticals. Preclinical evaluation using an animal experiment with an implanted tumor model is frequently used to examine the efficiency of the treatment method and to predict the treatment response before clinical trials. Here, we propose a mathematical model for evaluation of the tumor response in an implanted tumor model and apply it to the data obtained from the previous experiment of 211At treatment in a thyroid cancer mouse model. The proposed model is based on the set of differential equations, describing the kinetics of radiopharmaceuticals, the tumor growth, and the treatment response. First, the tumor growth rate was estimated from the control data without injection of 211At. The kinetic behavior of the injected radionuclide was used to estimate the radiation dose profile to the target tumor, which can suppress the tumor growth in a dose-dependent manner. An additional two factors, including the time delay for the reduction of tumor volume and the impaired recovery of tumor regrowth after the treatment, were needed to simulate the temporal changes of tumor size after treatment. Finally, the parameters obtained from the simulated tumor growth curve were able to predict the tumor response in other experimental settings. The model can provide valuable information for planning the administration dose of radiopharmaceuticals in clinical trials, especially to determine the starting dose at which efficacy can be expected with a sufficient safety margin.