Paper STRUCTURE OF A SINGLE MODEL TO DESCRIBE PLUTONIUM AND AMERICIUM DECORPORATION BY DTPA TREATMENTS P. Fritsch,* A. L. Se ´randour,* O. Gre ´my,* G. Phan, † N. Tsapis, ‡ E. Fattal, ‡ H. Benech, † J. R. Deverre, § and J. L. Poncy* Abstract—The aim of this study is to propose a single modeling structure to describe both plutonium and americium decorpo- ration by DTPA, which is based on hypotheses mostly validated by experimental data. Decorporation efficacy of extracellular retention depends on the concentration ratio of DTPA vs. actinides and varies in each compartment according to the amount of biological ligands and their affinity for actinides. By contrast, because the relatively long residence time of DTPA after its cell internalization and the stability of actinide-DTPA complexes, intracellular decorporation efficacy is mainly con- trolled by a DTPA/actinide ratio, which is specific to each retention compartment. Although the affinity of DTPA is much lower for americium than for plutonium, a larger decorporation of americium can be obtained, which is ex- plained by different biological ligands and/or their affinity for the actinide. Altogether, these results show that the relative contribution of intra vs. extracellular decorporation varies depending on the actinide, the chemical form of radionuclides, the galenic formulation of DTPA, and the treatment schedule. Health Phys. 99(4):553–559; 2010 Key words: 241 Am; biokinetics; modeling, biological; pharma- cokinetics INTRODUCTION IN THE case of accidental contamination with com- pounds containing plutonium, americium or curium, diethylenetriaminepenta-acetic acid can be administered as either CaNa 3 (Ca-DTPA) or ZnNa 3 (Zn-DTPA) salts to decrease committed radiological doses due to chronic alpha irradiation associated with long-term retention of the actinides. Human and animal data have shown that most of the chelating agent injected as a solution is rapidly excreted in urine (Stather et al. 1983; Durbin et al. 1997; Phan et al. 2005). Therefore, it is usually admitted that the transfer of DTPA within intracellular compartments is negligible with the decorporated actin- ides being located in extracellular spaces (see review by Me ´ne ´trier et al. 2005). However, in humans, the increase of actinide urinary excretion is not limited to the first day following treatment, 2–3% of the decorporation occurs later on with a gradual decrease described by an expo- nential function (T 1/2 7 d). This delayed excretion was considered to be due to retention of actinide-DTPA complexes within unidentified extracellular compart- ments of soft tissues (Hall et al. 1978). Actinide decor- poration also involves faecal excretion and, in the case of americium, after inhalation exposure to moderately sol- uble compounds (type M), efficacy of late DTPA therapy was clearly established in humans by a nearly complete liver decorporation, and the increase of bone retention could be prevented (Roedler et al. 1989). Recently, new experimental studies (Se ´randour and Fritsch 2008; Se ´randour et al. 2008; Fritsch et al. 2009) have been carried out in order to validate different hypotheses applied for modeling decorporation of pluto- nium by DTPA from human biological data (James et al. 2007; Fritsch et al. 2007; Breustedt et al. 2009). After systemic liver or lung contamination of rats associated with treatments by different galenic forms of Ca-DTPA at different doses, it was concluded that a significant amount of chelating agent enters within cells of soft tissues. This phenomenon leads to intracellular decorpo- ration which can be visualized by a delayed urinary excretion of Pu-DTPA. The rate of this slow excretion, which can be observed over 1 mo, decreases as an exponential function of time with half-life varying as a function of the intracellular retention compartment. This paper reports results of targeted experiments to characterize decorporation of americium by DTPA both by urinary and faecal excretion. It also summarizes the * CEA/DSV/iRCM/SREIT/LRT BP 12, 91680 Bruye `res le Cha ˆ- tel, France; † CEA/DSV/iBITEC/SPI, 91191 Gif sur Yvette, France; ‡ Univ Paris Sud, UMR CNRS 8612, 92296 Cha ˆtenay-Malabry, France; § CEA/DSV/i2BM/SHFJ, 91401 Orsay, France. For correspondence contact: P. Fritsch, CEA/DSV/iRCM/SREIT/ LRT BP 12, 91680 Bruye `res le Cha ˆtel, France, or email at paul. fritsch@cea.fr. (Manuscript accepted 18 September 2009) 0017-9078/10/0 Copyright © 2010 Health Physics Society DOI: 10.1097/HP.0b013e3181c1cccd 553