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, Rebecca J. Abergel
Abstract
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 Sc 3+ and Y 3+ 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. Sc 3+ and Y 3+ 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 86 Y-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.