Actinide chelation: biodistribution and in vivo complex stability of the targeted metal ions

Abstract

Because of the continuing use of nuclear fuel sources and heightened threats of nuclear weapon use, the amount of produced and released radionuclides is increasing daily, as is the risk of larger human exposure to fission product actinides. A rodent model was used to follow the in vivo distribution of representative actinides, administered as free metal ions or complexed with chelating agents including diethylenetriamine pentaacetic acid (DTPA) and the hydroxypyridinonate ligands 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO). Different metabolic pathways for the different metal ions were evidenced, resulting in intricate ligand- and metal-dependent decorporation mechanisms. While the three studied chelators are known for their unrivaled actinide decorporation efficiency, the corresponding metal complexes may undergo in vivo decomposition and release metal ions in various biological pools. This study sets the basis to further explore the metabolism and in vivo coordination properties of internalized actinides for the future development of viable therapeutic chelating agents.

Keywords::

• Actinides
• internal contamination
• decorporation
• in vivo distribution
• chelating agents

Acknowledgments

The authors are grateful to Prof. Kenneth N. Raymond and Dr. David K. Shuh for many helpful discussions and for their support of the actinide decorporation program at LBNL. This work was performed at the E. O. Lawrence Berkeley National Laboratory, a U.S. Department of Energy Laboratory under Contract No. DE-AC02-05CH11231, and presented at the 20th International Conference on Chelation, Grand Rapids, MI, USA, 22-25 October 2010.

Declaration of interest

This work was supported by National Institutes of Health grants 1RC2AI087604-01 and 5RC2AI087604-02 from the National Institute of Allergy and Infectious Diseases.