Specific Sequestering Agents for the Actinides: 4. Removal of 238 Pu(IV) from Mice by Sulfonated Tetrameric Catechoyl Amides

Durbin, Patricia W.; Jones, E; Raymond, Kenneth N.; Weitl, Frederick L.

doi:10.2307/3575394

Cited by 42 publications

(67 citation statements)

References 37 publications

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“…However, about twice as much 23 8 Pu remained in the skeleton in comparison with the amount found after administration of LICAM(C) with DTPA. It should be noted that according to Taylor (1976) and Durbin et al (1980Durbin et al ( , 1984 a) DFOA alone was less effective than DTPA in removing plutonium, while according to Smith (1964) and to our experience (Volf 1976, and table 2) it was the DFOA which was more effective. The apparent discrepancy may be due to differences in animal strain, to experimental conditions as well as to different effectiveness of the ligand preparations used.…”

Section: Discussionmentioning

confidence: 78%

“…Several of these agents were tested for their effectiveness in reducing the retention of plutonium in mice by Durbin et al (1980Durbin et al ( ,1984 and in reducing the retention of plutonium and americium in dogs and mice by Lloyd et al (1984). The authors of these studies have suggested that one compound, 3,4,3-LICAM(C) (N l , , N', N l°, N 4 -tetrakis(2,3-dihydroxy-4-carboxybenzoyl) tetraazatetradecane, tetrasodium salt), was a very promising new compound for plutonium decorporation when compared to the current agent of choice for the treatment of actinide contamination in man, CaNa 3 diethylenetriaminepentaacetic acid (DTPA).…”

Section: Introductionmentioning

confidence: 99%

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Chelation Therapy of Incorporated Plutonium-238 and Americium-241: Comparison of LICAM(C), DTPA and DFOA in Rats, Hamsters and Mice

Volf¹

1985

International Journal of Radiation Biology and Related Studies

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The carboxylated catechoylamide 3,4,3-LICAM(C) was tested for removal of 238Pu and 241Am from small laboratory rodents. The effectiveness of treatment was compared with that of two ligand preparations approved for clinical use: calcium-trisodium diethylenetriaminepentaacetate (DTPA) and desferrioxamine (DFOA). With early treatment and at the dosage used clinically for the decorporation of actinides with DTPA (30 mumol/kg body weight) LICAM(C) was superior to DFOA but when compared with DTPA, the effect of LICAM(C) on 238Pu was greater only in bone; as little as 1 mumol LICAM(C)/kg was as effective as 30 mumol DTPA/kg. However, in all animals treated with LICAM(C) there was a large increase in the 238Pu content of the kidney. With 241Am the effect of DTPA was always superior to that of LICAM(C). The best overall results early (1 day) after injection of 238Pu and 241Am were achieved by a combination of a single injection of LICAM(C) and DTPA with subsequent continuous administration of DTPA in drinking water. LICAM(C) affected the retention of 238Pu even if given orally; the data suggested that about 3 per cent of ingested LICAM(C) was absorbed. When the beginning of treatment was delayed, LICAM(C) became equally effective or less effective than DTPA even as far as 238Pu retention in bone was concerned, but it still increased the accumulation of 238Pu in the kidneys.

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Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Chelation Therapy of Incorporated Plutonium-238 and Americium-241: Comparison of LICAM(C), DTPA and DFOA in Rats, Hamsters and Mice

Volf¹

1985

International Journal of Radiation Biology and Related Studies

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“…The liver and skeleton of human, dog, and mouse appear to compete about equally for circulating plutonium (Stover et al 1959;Talbot et al 1993;Durbin et a]. 1980).…”

Section: Kinetics Of Iv-injected 238pu(iv) Citratementioning

confidence: 98%

“…The 238Pu(IV) citrate solution used in published studies of in vivo chelation of plutonium in mice was used to characterize the biokinetics (plasma clearance, tissue uptake) of 238Pu(IV) in the mouse: 4625 Bq mL-' of 2 3 8~u (~~) in a solution containing 0.008 mol L-' of sodium citrate and 0.14 mol L-' NaCl (referred to hereinafter as saline) (Durbin et al 1980(Durbin et al , 1989(Durbin et al , 1994Lloyd et al 1984;White et al 1988;Xu et al 1995 in saline; the 14C concentration was 1.1 X lo5 Bq mL--'. 3H-inulin was rinsed from the shipping container with saline, and the concentrations were 3.7 X lo5 Bq mL-' of and 2.2 pg mL-' of inulin.…”

Section: Materials and Detection Systemmentioning

confidence: 99%

“…All of the new multidentate ligands, composed of catecholate or hydroxypyridinonate binding units attached to flexible backbones, and with good aqueous solubility at pH 7.4 chelate and promote excretion of circulating plutonium, and many chelate other actinides. The most effective ligands promote significantly more actinide excretion in mice than an equimolar amount of CaNa,-DTPA and remove some actinide already deposited in liver, kidneys, and/or skeleton (Durbin et al 1980(Durbin et al , 1989(Durbin et al , 1994Lloyd et al 1984;White ct al. 1988;Xu et al 1995).…”

Section: Introductionmentioning

confidence: 97%

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Circulatory Kinetics of Intravenously Injected 238Pu(IV) Citrate and 14C-CaNa3-DTPA in Mice

Durbin

Kullgren²,

Schmidt³

1997

Health Physics

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New ligands for in vivo chelation of Pu(IV) are being synthesized and evaluated in mice for efficacy and toxicity. Biokinetic studies of the new ligands, CaNa3-DTPA, and Pu(IV) are major components of those investigations. Young adult female mice were injected intravenously (iv) with 3H-inulin, 14C-CaNa3-DTPA, or 238Pu(IV) citrate to provide baseline data for plasma clearance, tissue uptake, and excretion rates and to determine the dilution volume (VOD) and renal clearance rate (RC) of filterable substances. Published plasma clearance data for iv-injected 14C-CaNa3-DTPA and Pu(IV) citrate in Reference Man, dog, and rat were collected. Based on combined data for 3H-inulin and 14C-CaNa3-DTPA, VOD = 17% of body weight and RC = 18 mL kg(-1) min(-1) for mice. Retention of 14C-CaNa3-DTPA in the four species is proportional to body weight and inversely proportional to RC: Integrals of the retention of 14C-CaNa3-DTPA from R(t) = 1.0 to R(t) = 0.05 are 108, 43, 28, and 10 DF min, respectively, for Reference Man, dog, rat, and mouse. Clearances of iv-injected Pu(IV) citrate from plasma are in the same order: The plasma curve integrals from injection to 1440 min are 840, 640, 280, and 67 DF min, respectively, for Reference Man, dog, rat, and mouse. In mice, a large fraction of newly injected Pu(IV) is rapidly transferred to the interstitial water of bulk soft tissue (excluding liver and kidneys), from which it is cleared at the same rate as from the plasma. Rapid plasma clearance, escape into interstitial water (22%ID at 20 min), significant early urinary excretion (8%ID in 12 h), and prompt deposition in liver and skeleton (complete in 12 h) are evidence of inefficient binding to plasma protein (mainly transferrin) of newly injected Pu(IV) in mice. Conversely, slow plasma clearance, little early urinary excretion, and delayed deposition in liver and skeleton reflect more efficient binding by transferrin of newly injected Pu(IV) in Reference Man and dog. Pharmacokinetic parameters (effective dosage, effective concentration) of CaNa3-DTPA, alone or combined with plasma Pu(IV) integrals, yielded only qualitative predictions of the relative efficacies of CaNa3-DTPA therapy in four species. The need for improved models of Pu(IV) and ligand biokinetics and the suitability of the three animals for predicting chelation therapy outcomes in humans are discussed.

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Actinide-specific sequestering agents and decontamination applications

Raymond

Smith

1981

Structure and Bonding

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Specific Sequestering Agents for the Actinides: 4. Removal of 238 Pu(IV) from Mice by Sulfonated Tetrameric Catechoyl Amides

Cited by 42 publications

References 37 publications

Chelation Therapy of Incorporated Plutonium-238 and Americium-241: Comparison of LICAM(C), DTPA and DFOA in Rats, Hamsters and Mice

Chelation Therapy of Incorporated Plutonium-238 and Americium-241: Comparison of LICAM(C), DTPA and DFOA in Rats, Hamsters and Mice

Circulatory Kinetics of Intravenously Injected 238Pu(IV) Citrate and 14C-CaNa3-DTPA in Mice

Actinide-specific sequestering agents and decontamination applications

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