Developing a physiologically based approach for modeling plutonium decorporation therapy with DTPA

Abstract

Purpose: To develop a physiologically based compartmental approach for modeling plutonium decorporation therapy with the chelating agent Diethylenetriaminepentaacetic acid (Ca-DTPA/Zn-DTPA).

Materials and methods: Model calculations were performed using the software package SAAM II (©The Epsilon Group, Charlottesville, Virginia, USA). The Luciani/Polig compartmental model with age-dependent description of the bone recycling processes was used for the biokinetics of plutonium.

Results: The Luciani/Polig model was slightly modified in order to account for the speciation of plutonium in blood and for the different affinities for DTPA of the present chemical species. The introduction of two separate blood compartments, describing low-molecular-weight complexes of plutonium (Pu-LW) and transferrin-bound plutonium (Pu-Tf), respectively, and one additional compartment describing plutonium in the interstitial fluids was performed successfully.

Conclusions: The next step of the work is the modeling of the chelation process, coupling the physiologically modified structure with the biokinetic model for DTPA. Results of animal studies performed under controlled conditions will enable to better understand the principles of the involved mechanisms.

Keywords::

• Biokinetic modeling
• actinides
• plutonium
• DTPA
• chelation
• decorporation

Acknowledgements

The authors thank EURADOS for its continuous support and all members of Working Group 7 for the interesting and lively discussions. We would like to thank also Andrea Luciani (currently at IAEA, Vienna) for the many fruitful and valuable suggestions. The members of the Task Group ‘Towards a DTPA therapy model’ of EURADOS Working Group 7 are currently P. Bérard (CEA, France), E. Blanchardon (IRSN, France), B. Breustedt (KIT, Germany), P. Fritsch (CEA, France), A. Giussani (BfS, Germany), M. Kastl (Helmholtz Zentrum München and Technische Universität München, Germany), B. Leprince (CEA, France), and M. A. Lopez (CIEMAT, Spain).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. The travel and meeting costs of the Working Group are partially supported by EURADOS, and the work is conducted within the institutional research of the institutes to which the authors are affiliated.