2012
DOI: 10.1002/ddr.21020
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Significance of Single Variables in Defining Adequate Animal Models to Assess the Efficacy of New Radionuclide Decorporation Agents: Using the Contamination Dose as an Example

Abstract: Strategy, Management and Health PolicyEnabling Technology, Genomics, ProteomicsPreclinical ResearchPreclinical Development Toxicology, Formulation Drug Delivery, PharmacokineticsClinical Development Phases I‐III Regulatory, Quality, ManufacturingPostmarketing Phase IV Internal radioactive contamination can arise in different ways, from accidents affecting nuclear sites and industrial or medical sources, to the possible terrorist use of radiological dispersal devices. In all cases, internalized radionuclides … Show more

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Cited by 15 publications
(11 citation statements)
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“…The actinide decorporation efficacies of the two hydroxypyridinonate ligands 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO) have been investigated through many in vivo studies over the past three decades [14, 15, 20, 21, 24], in order to delineate the therapeutic potential of both experimental compounds. These experiments were designed to characterize radionuclide elimination enhancement after prompt or slightly delayed treatment with chelating agents, most often within the first 24 hours of the contamination event.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…The actinide decorporation efficacies of the two hydroxypyridinonate ligands 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO) have been investigated through many in vivo studies over the past three decades [14, 15, 20, 21, 24], in order to delineate the therapeutic potential of both experimental compounds. These experiments were designed to characterize radionuclide elimination enhancement after prompt or slightly delayed treatment with chelating agents, most often within the first 24 hours of the contamination event.…”
Section: Discussionmentioning
confidence: 99%
“…Those differences have been discussed previously and are presumably based on respective ligand and actinide-complex physico-chemical parameters such as solubility, lipophilicity, and ionization constants [15, 20, 21]. In addition, the biliary pathway is the main mode of elimination for 3,4,3-LI(1,2-HOPO) in mice, as demonstrated by high accumulation of 14 C-labeled 3,4,3-LI(1,2-HOPO) in the feces after either parenteral or oral administration [26].…”
Section: Discussionmentioning
confidence: 99%
“…On the other hand, the complex formed with the tetradentate 5-LIO(Me-3,2-HOPO) was not stable enough to be fully excreted (with 58 % of total excretion through the fecal pathway), as 14 % of the injected Cm was retained at 24 h. Such discrepancy in excretion patterns between acetate and hydroxypyridinonate ligands has been reported previously for other metal complexes, including Eu III , Am III , and Pu IV . [9,13,37,38] This result suggests ligand-dependent biochemical pathways in the metabolism of these complexes and ultimately in the mechanism of decorporation, probably owing to the respective ionization potential and membrane permeability properties of the ligands. Overall, these results corroborate the thermodynamic stability of the Cm III complexes of DTPA, 3,4,3-LI(1,2-HOPO), and 5-LIO(Me-3,2-HOPO): although all three ligands form highly stable complexes in vitro and in vivo, the octadentate hydroxypyridinonate ligand, 3,4,3-LI (1,2-HOPO), has a higher affinity for Cm III , which enhances its capability to compete with biological ligands such as proteins and bone matrices, as compared with DTPA and the tetradentate 5-LIO(Me-3,2-HOPO).…”
Section: Solution Thermodynamicsmentioning
confidence: 92%
“…However, it is unethical to evaluate the effi cacy of chelating agents in humans; therefore, animal models must be used to evaluate their effi cacies. New chelating agents or new formulations of existing chelating agents for plutonium are being developed recently (Jarvis et al 2012, Shankar et al 2012, Bunin et al 2013 approximately 30% of the injected activity was deposited in liver and 55% in skeleton (Markley et al 1964, Stevens et al 1975. Th e 239 Pu ϩ 4 content in skeleton to liver ratios varies from 1.7 -3.9 for rats and 1.5 -3.9 for dogs (Markley et al 1964, Stevens et al, 1975.…”
Section: Introductionmentioning
confidence: 98%