A 3,2-Hydroxypyridinone-based Decorporation Agent that Removes Uranium from Bones In Vivo

Xiaomei Wang, Xing Dai, Cen Shi, Jianmei Wan, Mark A. Silver, Linjuan Zhang, Lanhua Chen, Xuan Yi, Bizheng Chen, Duo Zhang, Kai Yang, Juan Diwu (), Jianqiang Wang, Yujie Xu, Ruhong Zhou (), Zhifang Chai and Shuao Wang ()
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Xiaomei Wang: Soochow University
Xing Dai: Soochow University
Cen Shi: Soochow University
Jianmei Wan: Soochow University
Mark A. Silver: Soochow University
Linjuan Zhang: University of Chinese Academy of Sciences
Lanhua Chen: Soochow University
Xuan Yi: Soochow University
Bizheng Chen: Soochow University
Duo Zhang: Soochow University
Kai Yang: Soochow University
Juan Diwu: Soochow University
Jianqiang Wang: University of Chinese Academy of Sciences
Yujie Xu: Soochow University
Ruhong Zhou: Soochow University
Zhifang Chai: Soochow University
Shuao Wang: Soochow University

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract Searching for actinide decorporation agents with advantages of high decorporation efficiency, minimal biological toxicity, and high oral efficiency is crucial for nuclear safety and the sustainable development of nuclear energy. Removing actinides deposited in bones after intake is one of the most significant challenges remaining in this field because of the instantaneous formation of highly stable actinide phosphate complexes upon contact with hydroxyapatite. Here we report a hydroxypyridinone-based ligand (5LIO-1-Cm-3,2-HOPO) exhibiting stronger affinity for U(VI) compared with the reported tetradentate hydroxypyridinone ligands. This is further revealed by the first principles calculation analysis on bonding between the ligand and uranium. Both in vitro uranium removal assay and in vivo decorporation experiments with mice show that 5LIO-1-Cm-3,2-HOPO can remove uranium from kidneys and bones with high efficiencies, while the decorporation efficiency is nearly independent of the treatment time. Moreover, this ligand shows a high oral decorporation efficiency, making it attractive for practical applications.

Date: 2019
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DOI: 10.1038/s41467-019-10276-z

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