Developing scandium and yttrium coordination chemistry to advance theranostic radiopharmaceuticals

Korey P Carter; Gauthier J-P Deblonde; Trevor D Lohrey; Tyler A Bailey; Dahlia D An; Katherine M Shield; Wayne W Lukens Jr; Rebecca J Abergel

doi:10.1038/s42004-020-0307-0

Developing scandium and yttrium coordination chemistry to advance theranostic radiopharmaceuticals

Commun Chem. 2020 May 15;3(1):61. doi: 10.1038/s42004-020-0307-0.

Authors

Korey P Carter^#¹, Gauthier J-P Deblonde^#^{1

2}, Trevor D Lohrey^{1

3}, Tyler A Bailey^{1

4}, Dahlia D An¹, Katherine M Shield^{1

4}, Wayne W Lukens Jr¹, Rebecca J Abergel^{5

6}

Affiliations

¹ Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, United States.
² Glenn T. Seaborg Institute, Physical and Life Sciences, Lawrence Livermore National Laboratory, Livermore, CA, 94550, United States.
³ Department of Chemistry, University of California, Berkeley, CA, 94720, United States.
⁴ Department of Nuclear Engineering, University of California, Berkeley, CA, 94709, United States.
⁵ Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, United States. [email protected].
⁶ Department of Nuclear Engineering, University of California, Berkeley, CA, 94709, United States. [email protected].

^# Contributed equally.

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.