Influence of common decorporation agents on the speciation of trivalent f-elements in serum – a luminescence spectroscopic study

The accidental release of radionuclides, especially actinides (An), in a nuclear facility or in the environment increases the risk of incorporation of these elements into the human body. Irrespective of the uptake pathway, via inhalation, ingestion, or through wounds or the skin, An are resorbed and transported by the bloodstream. Eventually, they are deposited in target organs (e.g., bone, liver or kidney) or partially excreted with urine or faeces. Fast and effective decorporation or chelation therapy is very important to minimize the health risk. To improve decorporation efficiency by choosing the right chelating agent or by designing new efficient chelators for different An, the understanding of their chemical speciation on a molecular level is crucial.
In this study, we investigate the chemical speciation of Cm(III) (as representative of An) and Eu(III) (as non-radioactive analogue for trivalent An) in blood serum. Subsequently, the alterations in speciation after spiking with common chelating agents often used for decorporation purposes, such as ethylenediaminetetraacetic acid (EDTA), or diethylenetriaminepentaacetic acid (DTPA), were studied and compared to biological ligands, such as citrate. Time-resolved laser-induced fluorescence spectroscopy (TRLFS) was used to perform the speciation investigations. Thermodynamic calculations were carried out to support the experimental results.
The dominant chemical species of Eu in serum were identified by comparing the Eu luminescence spectra and lifetimes in serum with those obtained in reference solutions with individual components of the serum, such as the proteins albumin and transferrin as well as the inorganic anions phosphate and carbonate. Linear combination fitting analysis (LCFA) on the sample spectra indicated that Eu is mainly coordinated by albumin (~50 %) and transferrin (~35 %), and to a lesser extent by inorganic anions like carbonate (~15 %).
The shape of the Eu luminescence spectrum in serum was only slightly influenced by adding citrate and EDTA, whereas the shapes of the pure ligand spectra differ strongly. This indicates that the speciation of Eu in serum was only slightly changed by these ligands. In contrast, DTPA caused a splitting of both the 7F1 and 7F2 peak, which is very similar to the Eu spectrum with the pure DTPA ligand, indicating a strong change of the Eu speciation in serum towards Eu-DTPA complexation. LCFA indicated that about 50 % of the Eu was coordinated by DTPA. The luminescence lifetimes and thermodynamic calculations as well as the Cm luminescence data show similar tendencies. Our results follow the trend of the respective complex stability constants of Am(III) complexes with chelating agents and the findings from 241Am experiments with animals.
This study combining TRLFS and thermodynamic calculations demonstrates a fast and easy way to screen the effect of several chelating agents towards (luminescent) An in vitro. In future, this could be a useful tool to improve decorporation methods.