The Distribution and Excretion of Injected Uranium

Neuman, W. F.; Fleming, R.W.; Dounce, Alexander L.; Carlson, A.B.; O’Leary, James W.; Mulryan, B.J.

doi:10.1016/s0021-9258(18)57445-7

Cited by 34 publications

(4 citation statements)

References 12 publications

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“…The complex [UO 2 (CHXhox)] was omitted from this study because of its poor aqueous solubility, which resulted in its precipitation in the circulatory system upon injection, causing lethality. As observed in previous studies, the administration of [UO 2 (NO 3 ) 2 ]·6H 2 O results in a significant accumulation of uranium in bone (Figure a), as well as the spleen and kidneys. − Other bone-seeking heavy radionuclides, such as radium, , also localize to the spleen in small animals. In this study, renal retention of uranium was lower than expected based on related biodistribution experiments.…”

Section: Resultssupporting

confidence: 57%

Stable Chelation of the Uranyl Ion by Acyclic Hexadentate Ligands: Potential Applications for ²³⁰U Targeted α-Therapy

et al. 2022

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Uranium-230 is an α-emitting radionuclide with favorable properties for use in targeted α-therapy (TAT), a type of nuclear medicine that harnesses α particles to eradicate cancer cells. To successfully implement this radionuclide for TAT, a bifunctional chelator that can stably bind uranium in vivo is required. To address this need, we investigated the acyclic ligands H 2 dedpa, H 2 CHXdedpa, H 2 hox, and H 2 CHXhox as uranium chelators. The stability constants of these ligands with UO 2 2+ were measured via spectrophotometric titrations, revealing log β ML values that are greater than 18 and 26 for the "pa" and "hox" chelators, respectively, signifying that the resulting complexes are exceedingly stable. In addition, the UO 2 2+ complexes were structurally characterized by NMR spectroscopy and X-ray crystallography. Crystallographic studies reveal that all six donor atoms of the four ligands span the equatorial plane of the UO 2 2+ ion, giving rise to coordinatively saturated complexes that exclude solvent molecules. To further understand the enhanced thermodynamic stabilities of the "hox" chelators over the "pa" chelators, density functional theory (DFT) calculations were employed. The use of the quantum theory of atoms in molecules revealed that the extent of covalency between all four ligands and UO 2 2+ was similar. Analysis of the DFT-computed ligand strain energy suggested that this factor was the major driving force for the higher thermodynamic stability of the "hox" ligands. To assess the suitability of these ligands for use with 230 U TAT in vivo, their kinetic stabilities were probed by challenging the UO 2 2+ complexes with the bone model hydroxyapatite (HAP) and human plasma. All four complexes were >95% stable in human plasma for 14 days, whereas in the presence of HAP, only the complexes of H 2 CHXdedpa and H 2 hox remained >80% intact over the same period. As a final validation of the suitability of these ligands for radiotherapy applications, the in vivo biodistribution of their UO 2 2+ complexes was determined in mice in comparison to unchelated [UO 2 (NO 3 ) 2 ]. In contrast to [UO 2 (NO 3 ) 2 ], which displays significant bone uptake, all four ligand complexes do not accumulate in the skeletal system, indicating that they remain stable in vivo. Collectively, these studies suggest that the equatorial-spanning ligands H 2 dedpa, H 2 CHXdedpa, H 2 hox, and H 2 CHXhox are highly promising candidates for use in 230 U TAT.

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Section: Resultssupporting

confidence: 57%

Stable Chelation of the Uranyl Ion by Acyclic Hexadentate Ligands: Potential Applications for ²³⁰U Targeted α-Therapy

et al. 2022

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“…This is consistent the study of Kurttio et al 17 . They observed that about 80 to 90 deposition product of uranium in the bones deposited in the mineral structure of bone and deposition of the mechanism of uranium is UO 2 2+ interacted with the bone mineral phase 18 .…”

Section: Uranium Speciation and Distribution In Bonesmentioning

confidence: 99%

Biodistribution of Uranium in Mice and Influencing Factor Preliminary Discussion

Deng¹,

Hou²,

Liang³

2014

Asian J. Chem.

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The general objective of our work was to preliminary discuss the relationship between uranium(VI) distribution in mice and the speciation of uranium in blood plasma and urine. The results show that, mice were injected with depleted uranium (DU) (5 mg/kg), the important uranium deposit sites are bones, kidneys, liver and spleen. Excretion of uranium mainly through kidney and the concentration of uranium in the liver and spleen have two peaks with time passed. Computer simulation shows that the major uranium species were uranium complex ions at normal blood plasma pH value, which explain the animal experiment phenomenon that uranium removed faster in the blood and the species of uranium in the plasma blood related to the total uranium concentration. The formation of souble uranyl ion with phosphate radical is high solubility solid material, resulting in uranium long-term deposition in bone. Computer simulation also shows the solid phase as (UO2)3(PO4)2•4H2O appeared in the urine, which are toxic to kidneys.

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“…This shell contains many entrapped ions, including those of calcium, phosphate, and even organic complexes such as citrate, and may also bind other ions such as those of radium and uranium. [73][74] Ionic exchange within the hydration shell is likely to be a necessary precursor to exchange within the crystal matrix itself and is also likely to be easily reversed. Aluminium trapped in this way is, therefore, likely to be mobile and subject to back exchangefirstly with complexes in the tissue fluids close to bone surfaces and then with transferrin in plasma.…”

Section: Skeletal Aluminium Depositsmentioning

confidence: 99%

The biological behaviour and bioavailability of aluminium in man, with special reference to studies employing aluminium-26 as a tracer: review and study update

2004

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Until 1990 biokinetic studies of aluminium metabolism and biokinetics in man and other animals had been substantially inhibited by analytical and practical difficulties. Of these, the most important are the difficulties in differentiating between administered aluminium and endogenous aluminium-especially in body fluids and excreta and the problems associated with the contamination of samples with environmental aluminium. As a consequence of these it was not possible to detect small, residual body burdens of the metal following experimental administrations. Consequently, many believed aluminium to be quantitatively excreted within a short time of uptake in all, but renal-failure patients. Nevertheless, residual aluminium deposits in a number of different organs and tissues had been detected in normal subjects using a variety of techniques, including histochemical staining methods. In order to understand the origins and kinetics of such residual aluminium deposits new approaches were required. One approach taken was to employ the radioisotope (67)Ga as a surrogate, but this approach has been shown to be flawed-a consequence of the different biological behaviours of aluminium and gallium. A second arose from the availability, in about 1990, of both (26)Al-a rare and expensive isotope of aluminium-and accelerator mass spectrometry for the ultra-trace detection of this isotope. Using these techniques the basic features of aluminium biokinetics and bioavailability have been unravelled. It is now clear that some aluminium is retained in the body-most probably within the skeleton, and that some deposits in the brain. However, most aluminium that enters the blood is excreted in urine within a few days or weeks and the gastrointestinal tract provides an effective barrier to aluminium uptake. Aspects of the biokinetics and bioavailability of aluminium are described below.

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The Distribution and Excretion of Injected Uranium

Cited by 34 publications

References 12 publications

Stable Chelation of the Uranyl Ion by Acyclic Hexadentate Ligands: Potential Applications for ²³⁰U Targeted α-Therapy

Stable Chelation of the Uranyl Ion by Acyclic Hexadentate Ligands: Potential Applications for ²³⁰U Targeted α-Therapy

Biodistribution of Uranium in Mice and Influencing Factor Preliminary Discussion

The biological behaviour and bioavailability of aluminium in man, with special reference to studies employing aluminium-26 as a tracer: review and study update

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The Distribution and Excretion of Injected Uranium

Cited by 34 publications

References 12 publications

Stable Chelation of the Uranyl Ion by Acyclic Hexadentate Ligands: Potential Applications for 230U Targeted α-Therapy

Stable Chelation of the Uranyl Ion by Acyclic Hexadentate Ligands: Potential Applications for 230U Targeted α-Therapy

Biodistribution of Uranium in Mice and Influencing Factor Preliminary Discussion

The biological behaviour and bioavailability of aluminium in man, with special reference to studies employing aluminium-26 as a tracer: review and study update

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Stable Chelation of the Uranyl Ion by Acyclic Hexadentate Ligands: Potential Applications for ²³⁰U Targeted α-Therapy

Stable Chelation of the Uranyl Ion by Acyclic Hexadentate Ligands: Potential Applications for ²³⁰U Targeted α-Therapy