A Model of Time-dependent Biodistribution of 153Sm-Maltolate Complex and Free 153Sm Cation Using Compartmental Analysis

Abstract

Introduction Compartmental analysis allows the mathematical separation of tissues and organs to determine activity concentration in each point of interest. Biodistribution studies on humans are costly and complicated, whereas such assessments can be easily performed on rodents. In this study, we aimed to develop a pharmacokinetic model of 153Sm-maltolate complex as a novel therapeutic agent and free 153Sm cation in normal rats using compartmental analysis to evaluate the behavior of this complex. Materials and Methods We developed a physiologically-based pharmacokinetic model for scaling up the activity concentration in each organ with respect to time. In the mathematical model, physiological parameters including organ volume, blood flow rate, and vascular permeability were used. The compartments (organs) were connected anatomically, which allowed the use of scale-up techniques to predict new complex distribution in each body organ. Results The concentration of 153Sm-maltolate complex and free 153Sm cation in various organs was measured at different time intervals. The time-dependent behavior of the biodistribution of these two radiotracers was modeled, using compartmental analysis; the detected behaviors were drawn as a function of time. Conclusion The variation in radiopharmaceutical concentration in organs of interest could be described by summing seven to nine exponential terms, which approximated the experimental data with a precision of > 1% in comparison with the original data from animal studies.