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Developing scandium and yttrium coordination chemistry to advance theranostic radiopharmaceuticals
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https://doi.org/10.1038/s42004-020-0307-0Abstract
The octadentate siderophore analog 3,4,3-LI(1,2-HOPO), denoted 343-HOPO hereafter, is known to have high affinity for both trivalent and tetravalent lanthanide and actinide cations. Here we extend its coordination chemistry to the rare-earth cations Sc3+ and Y3+ and characterize fundamental metal-chelator binding interactions in solution via UV-Vis spectrophotometry, nuclear magnetic resonance spectroscopy, and spectrofluorimetric metal-competition titrations, as well as in the solid-state via single crystal X-ray diffraction. Sc3+ and Y3+ binding with 343-HOPO is found to be robust, with both high thermodynamic stability and fast room temperature radiolabeling, indicating that 343-HOPO is likely a promising chelator for in vivo applications with both metals. As a proof of concept, we prepared a 86Y-343-HOPO complex for in vivo PET imaging, and the results presented herein highlight the potential of 343-HOPO chelated trivalent metal cations for therapeutic and theranostic applications.
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