4.7 Article

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

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PHARMACEUTICS
卷 13, 期 11, 页码 -

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MDPI
DOI: 10.3390/pharmaceutics13111830

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radionuclides; kinetics of decorporation; compartmental vs; diffusional models; square-root law

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The study investigated the decorporation kinetics of internal radionuclide contamination and found that mono- and bi-compartmental decorporation kinetics models are applicable for rapid intervention, while a diffusion model of the radionuclide from tissues to blood is better for describing decorporation kinetics after more than ten days post treatment. The square-root law for describing the Zn-65 decorporation predicts a slower release rate than exponential equations and better explains the long persistence of radionuclides in the living body.
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 (ZnCl2)-Zn-65 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 Zn-65 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.

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