Compartmental Analysis to Predict the Biodistribution of [166Ho]- DOTA-Bevacizumab for Targeted Radiotherapy Purpose

Abstract

Purpose- The main aim of this study was to develop the pharmacokinetic model for the colorectal cancer’s complex 166Ho-DOTA-Bevacizumab in normal and tumoral rats to analyze of behavior as a new composition for diagnosing and treatment. The use of compartmental analysis allows a mathematical separation of tissues and organs to determine the concentration of activity in each fraction of interest. Biodistribution studies are expensive and difficult to carry out in humans, but such data can be obtained easily in rodents and rat.

Methods- We have developed a physiologically based pharmacokinetic model for scaling up activity concentration in each organ versus time. The mathematical model uses physiological parameters including organ volumes, blood flow rates, and vascular permeability. The compartments (organs) are connected anatomically. This allows the use of scale-up techniques to predict the new complex distribution in humans in each organ.

Results- The concentration of the new complex was measured in various organs at the different times. The behavior of the complex (166Ho-DOTA-Bevacizumab) was modeled as a function of time in various organs. These data was diagrammed as a time function in the separated graph for each organ between 2-96 hours after injection.

Conclusion- The variation of integrated uptake in organs is described with summationof 6-9 exponential terms and it approximated experimental data with 1-2 %precision. As shown in the diagram the mathematical model and biodistribution data in an experiment has a good joint and coincidence and it is a good sign to save time and cost in the next other researches.