In Vitro and In Vivo Assessment of Plutonium Speciation and Decorporation in Blood and Target Retention Tissues after a Systemic Contamination followed by an Early Treatment with DTPA

Sérandour, A. L., Grémy, O., Fréchou, M., Renault, D., Poncy, J. L. and Fritsch, P. In Vitro and In Vivo Assessment of Plutonium Speciation and Decorporation in Blood and Target Retention Tissues after a Systemic Contamination followed by an Early Treatment with DTPA. Radiat. Res. 170, 208–215 (2008). This study identifies the main sources of systemic plutonium decorporated in the rat after DTPA i.v. at the dose recommended for humans (30 μmol kg−1). For this purpose, standard biokinetic approaches are combined to plasma ultrafiltration for separation of plutonium complexes according to their molecular weight. In vitro studies show that at the recommended DTPA dose, less than 5% of the plasma plutonium of contaminated rats can be displaced from high-molecular-weight ligands. After i.v. administration of Pu-DTPA, early ultrafiltrability of plutonium in plasma decreases with total DTPA dose, which is associated with an increase in plutonium bone retention. This demonstrates the instability of Pu-DTPA complexes, injected in vivo, below the minimal Ca-DTPA dose of 30 μmol kg−1. Plutonium biokinetics is compared in rats contaminated by plutonium-citrate i.v. and treated or not with DTPA after 1 h. No significant decrease in plasma plutonium is observed for the first hour after treatment, and the fraction of low-molecular-weight plutonium in plasma is nearly constant [5.4% compared with 90% in Pu-DTPA i.v. (30 μmol kg−1) and 0.7% in controls]. Thus plutonium decorporation by DTPA is a slow process that mainly involves retention compartments other than the blood. Plutonium-ligand complexes formed during plutonium deposition in the retention organs appear to be the main source of decorporated plutonium.