Experimental Evaluation of 65Zn Decorporation Kinetics Following Rapid and Delayed Zn-DTPA Interventions in Rats. Biphasic Compartmental and Square-Root Law Mathematical Modeling

Abstract

The decorporation kinetics of internal radionuclide contamination is a long-term treatment raising modeling, planning, and managing problems, especially in the case of late intervention when the radiotoxic penetrated the deep compartments. The decorporation effectiveness of the highly radiotoxic 65ZnCl2 by Zn-DTPA (dosed at 3.32 mg and 5 mg/0.25 mL/100 g body weight) was investigated in Wistar male rats over a ten-day period under various treatments (i.e., as a single dose before contamination; as a single dose before and 24 h after contamination; and as daily administrations for five consecutive days starting on day 12 after contamination). The radioactivity was measured using the whole-body counting method. Mono- and bi-compartmental decorporation kinetics models proved applicable in the case of a rapid intervention. It was found that a diffusion model of the radionuclide from tissues to blood better describes the decorporation kinetics after more than ten days post treatment, and the process has been mathematically modeled as a diffusion from an infinite reservoir to a semi-finite medium. The mathematical solution led to a square-root law for describing the 65Zn decorporation. This law predicts a slower release than exponential or multiexponential equations, and could better explain the very long persistence of radionuclides in the living body. Splitting data and modeling in two steps allows a better understanding, description and prediction of the evolution of contamination, a separate approach to the treatment schemes of acute and chronic contamination.