Spatial distribution of uranium in mice kidneys detected by laser ablation inductively coupled plasma mass spectrometry

Jim, Venessa; LaViolette, Corinne M.; Briehl, Margaret M.; Ingram, Jani C.

doi:10.17145/jab.17.007

Cited by 4 publications

(2 citation statements)

References 19 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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“…Unfortunately, the limited access to these analytical techniques limits considerably its daily use for routine analysis [18]. To the author's knowledge, a single work has been published recently for the semi-quantitative analysis of uranium by LA-ICP-MS in mice kidneys [19] due to the lack of an appropriate internal standard. In this work, LA-ICP-MS has been employed for mapping and quantifying uranium in histological tissue sections of rat kidney.…”

Section: Introductionmentioning

confidence: 99%

A novel calibration strategy based on internal standard–spiked gelatine for quantitative bio-imaging by LA-ICP-MS: application to renal localization and quantification of uranium

et al. 2020

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Mass spectrometry imaging (MSI) using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been employed for the elemental bio-distribution and quantification of uranium (U) in histological tissue sections of rodent kidneys. Kidneys were immediately immersed into 4% paraformaldehyde (PFA) solution for 24 h, Tissue-Tek O.C.T. Compound embedded and stored at − 80°C until cutting in a cryostat, and mounted in gel-covered glass slides. In order to assure complete ablation of sample, sample preparation and laser conditions were carefully optimized. In this work, a new analytical methodology is presented for performing quantitative laser ablation analyses based on internal standard (thulium, Tm)-spiked gelatine (10% m/v) for correction of matrix effects, lack of tissue homogeneity, and instrumental drift. In parallel, matrix-matched laboratory standards, dosed at different concentrations of U, were prepared from a pool of rat kidneys. The quantitative images of cryosections revealed heterogeneous distribution of uranium within the renal tissue, because the cortical concentration was up to 120fold higher than the medullary concentration.

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Assessment of uranium concentration in blood of Iraqi females diagnosed with breast cancer

Ahmed

Mohammed

2020

Radiat Environ Biophys

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Spatial distribution of uranium in mice kidneys detected by laser ablation inductively coupled plasma mass spectrometry

Cited by 4 publications

References 19 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

A novel calibration strategy based on internal standard–spiked gelatine for quantitative bio-imaging by LA-ICP-MS: application to renal localization and quantification of uranium

Assessment of uranium concentration in blood of Iraqi females diagnosed with breast cancer

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Spatial distribution of uranium in mice kidneys detected by laser ablation inductively coupled plasma mass spectrometry

Cited by 4 publications

References 19 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

A novel calibration strategy based on internal standard–spiked gelatine for quantitative bio-imaging by LA-ICP-MS: application to renal localization and quantification of uranium

Assessment of uranium concentration in blood of Iraqi females diagnosed with breast cancer

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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