Use of an Acellular Assay to Study Interactions between Actinides and Biological or Synthetic Ligands

Abstract

Speciation of actinides, and more particularly bioligand-binding ability, influences in vivo behavior. Understanding these interactions is essential for estimation of radiological dose and improvement of decorporation strategies for accidentally contaminated victims. Because the handling of actinides imposes overwhelming difficulties, in vitro assays carried out in physiological conditions are lacking and data regarding such interactions are scarce. In this study, we used a bi-compartmental and dynamic assay, providing physiological conditions (presence of inorganic ions, pH, temperature) to explore interactions between the actinides plutonium (Pu) and americium (Am) and endogenous (proteins transferrin and ferritin) or exogenous ligands (the chelating agent diethylenetriaminpentaacetic acid, DTPA). In this assay, an agarose gel represents the retention compartment of actinides and a dynamic fluid phase, the transfer compartment. The proportion of actinides transferred from static to dynamic phase reflects interactions between Pu/Am and various ligands. The results show differences in the formation of actinide-protein or actinide-DTPA complexes in physiologically relevant media depending on which ligand is present and where. We observed differential behavior for Pu and Am similar to in vivo studies. Thus, our assay may be used to determine the ability of various actinides to interact with specific proteins or with drug candidates for decorporation in complex physiologically relevant environments.

Take a Swipe at Actinide Bioavailability: Application of a New In Vitro Method

“…In addition, the medium used is a simple salt solution where the main constituent is sodium chloride (140 mM). Previous experiments in this laboratory as well as others have shown that the type of media may influence dissolution ( Ansoborlo et al 1999 ; Aladova et al 2007 ; Bauer et al 2012 ; Garger et al 2013 ; Griffiths et al 2016 ; Van der Meeren et al 2019 , 2022a ). The original report concerned the classification using Ringer’s solution where again the basic constituent is sodium chloride ( Khokhryakov et al 1998 ).…”

“…In this model, different actinides are incorporated into an agarose gel called the static phase and the transfer of activity to the external medium called the dynamic phase is monitored ( Griffiths et al 2016 ; Van der Meeren et al 2019 ). In this approach both phases may be modified to represent fluid compartments (blood, synovial fluid, sweat) or retention compartments (bone, lungs, intracellular) ( Griffiths et al 2016 ; Van der Meeren et al 2022a ). Moreover, this model was shown to correlate well with in vivo data from the laboratory using actinides prepared from the same stocks ( Griffiths et al 2016 ).…”