Abstract

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.

Radionuclide pairs 44Sc/47Sc and 86Y/90Y possess great promise in the development of theranostic agents, but realizing the full potential of these isotopes necessitates improving rare-earth chelation chemistry. Here the authors show that a hydroxypyridinone-based ligand is a promising candidate for applications in this arena.

Details

Title
Developing scandium and yttrium coordination chemistry to advance theranostic radiopharmaceuticals
Author
Carter, Korey P 1 ; Deblonde, Gauthier J-P 2   VIAFID ORCID Logo  ; Lohrey, Trevor D 3 ; Bailey, Tyler A 4 ; An, Dahlia D 1   VIAFID ORCID Logo  ; Shield, Katherine M 4 ; Lukens, Wayne W, Jr 1 ; Abergel, Rebecca J 4 

 Lawrence Berkeley National Laboratory, Chemical Sciences Division, Berkeley, United States (GRID:grid.184769.5) (ISNI:0000 0001 2231 4551) 
 Lawrence Berkeley National Laboratory, Chemical Sciences Division, Berkeley, United States (GRID:grid.184769.5) (ISNI:0000 0001 2231 4551); Physical and Life Sciences, Lawrence Livermore National Laboratory, Glenn T. Seaborg Institute, Livermore, United States (GRID:grid.250008.f) (ISNI:0000 0001 2160 9702) 
 Lawrence Berkeley National Laboratory, Chemical Sciences Division, Berkeley, United States (GRID:grid.184769.5) (ISNI:0000 0001 2231 4551); University of California, Department of Chemistry, Berkeley, United States (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878) 
 Lawrence Berkeley National Laboratory, Chemical Sciences Division, Berkeley, United States (GRID:grid.184769.5) (ISNI:0000 0001 2231 4551); University of California, Department of Nuclear Engineering, Berkeley, United States (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
23993669
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2403300736
Copyright
© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.