Search

The article discusses a study that proposes a single model for the decorporation of americium and plutonium through diethylene triamine pentaacetic acid (DTPA) therapy. The efficacy of the decorporation is influenced by DTPA ratio to the actinides. A higher decorporation of americium may be obtained by the affinity of the ligands to the actinide. The variation in the decorporation is influenced by the actinide, radionuclide, the dose of the DTPA and schedule of treatments.

Purpose : To modify the distribution of the chelating agent diethylene triamine pentaacetic acid (DTPA) by using a formulation approach with liposomes in order to match the in vivo distribution of plutonium (Pu) and, as a consequence, to improve actinide decorporation. Materials and methods : DTPA was encapsulated in conventional and stealth liposomes. Their pharmacokinetics and ability to remove Pu were evaluated in rats 2 and 16 days after a single intravenous treatment given 2 h after contamination with colloidal Pu ( 239 Pu phytate) or with soluble Pu ( 238 Pu citrate). Results : Both formulations induced major pharmacokinetic modifications in rats, allowing an accumulation of [ 14 C]-DTPA mainly in the liver and secondarily (for stealth liposomes) in bone and spleen. These modifications were associated with major increases in urine elimination and with a decrease in skeletal Pu deposition, depending of the nature of the Pu contaminant. After contamination by Pu phytate, conventional liposomes of DTPA (6 µ mol kg -1 ) were as efficient as free DTPA (30 µ mol kg -1 ) in maintaining the Pu content in the femur below 4.3% of the injected dose after 16 days, a 3.6-fold reduction compared with free DTPA (4 µ mol kg -1 ) treatment or without treatment. Conclusions : A formulation approach with liposomes appears to be a powerful tool to improve the efficiency of Pu chelating agents in vivo . [ABSTRACT FROM AUTHOR]

Abstract: DTPA, an actinide chelating agent, has demonstrated its ability to complex plutonium (Pu) and to facilitate its urinary excretion after internal contamination. This process, known as decorporation is crucial to diminish the burden of Pu in the body. The ability to deliver a chelating agent directly to the alveolar region may increase its local concentration as compared to systemic delivery and therefore increase the extent of decorporation. Second, inhalation offers the potential for needle-free, systemic delivery of small molecules and would be convenient in case of nuclear accident as a first pass emergency treatment. To benefit from the improvement of inhalation technology, we have formulated DTPA into porous particles by spray-drying with dl-Leucine, DPPC and ammonium bicarbonate. The optimized particles possess a volume mean geometric diameter around 4.5 μm and crumpled paper morphology. The in vitro aerodynamic evaluation shows that about 56% of the powder should deposits in the lungs, with about 27% in the alveolar region, an improvement as compared with the micronized powder available with the Spinhaler®. After pulmonary administration to rats contaminated with PuO2, a 3-fold increase of the Pu urinary excretion was observed, but the dissolution of PuO2 in the lungs was not enhanced. [Copyright &y& Elsevier]

Abstract: The aim of the study was to demonstrate that decorporation of 238Pu is achieved more efficiently by an optimized liposomal formulation of diethylene triamine pentaacetic acid (DTPA) than by the usual free DTPA treatment. The optimized formulation consisted of polyethylene glycol-coated stealth® liposomes with a mean diameter of 100 nm (SL-100 nm). Rats were intravenously injected with various Pu-phytate salt solutions in order to test different contamination conditions (activity and salt concentration) impacting liver kinetics and skeletal uptake of Pu. All treatments were given intravenously 1 h after contamination. Efficiency was evaluated 24 h, 7, 16 or 30 days later through their ability to promote Pu elimination and to reduce Pu burden in the skeleton and liver, the main organs of Pu deposition and radiotoxicological effects. Whatever the conditions of contaminations, a single injection of SL-100 nm (3.2 μmol kg–1 DTPA) boosted urinary elimination of Pu to above 90% of the injected dose. In addition, liposomes strongly and significantly reduced the Pu burden of the liver and skeleton even 30 days after a single treatment: a dose of 0.3 μmol kg–1 induced the same skeletal Pu reduction as four injections of free DTPA (30 μmol kg–1). A log dose–effect relation was found with SL-100 nm DTPA and Pu excretion in urine or Pu burden in the studied organs (liver, femurs, spleen and kidneys). This efficacy was attributed to an optimized targeting of DTPA to the main Pu retention organs and especially the liver. [Copyright &y& Elsevier]