Voicu Victor, Jiquidi Marilena, Mircioiu Constantin, Sandulovici Roxana, Nicolescu Adrian
Department of Clinical Pharmacology and Toxicology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050477 Bucharest, Romania.
Army Center for Medical Research, 021051 Bucharest, Romania.
Pharmaceutics. 2021 Nov 2;13(11):1830. doi: 10.3390/pharmaceutics13111830.
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 ZnCl 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 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.
体内放射性核素污染的促排动力学是一种长期治疗方法，会引发建模、规划和管理方面的问题，尤其是在进行后期干预时，此时放射毒性物质已渗透到深部组织。研究了在不同治疗方案下（即污染前单次给药；污染前单次给药及污染后24小时单次给药；污染后第12天开始连续五天每日给药），Zn-DTPA（剂量为3.32毫克和5毫克/0.25毫升/100克体重）对Wistar雄性大鼠体内高放射毒性的ZnCl的促排效果。采用全身计数法测量放射性。单室和双室促排动力学模型在快速干预情况下被证明是适用的。研究发现，放射性核素从组织到血液的扩散模型能更好地描述治疗后十多天的促排动力学，并且该过程已被数学建模为从无限储库到半无限介质的扩散。数学解得出了描述锌促排的平方根定律。该定律预测的释放速度比指数或多指数方程慢，并且能更好地解释放射性核素在生物体内的长期留存现象。分两步对数据进行拆分和建模，能够更好地理解、描述和预测污染的演变情况，为急性和慢性污染的治疗方案提供了一种独立的方法。
