丁香园AV

Abstract

The interest and use of radiometals in radiopharmaceutical development has considerably increased over the last few decades, owing in part to their diverse chemistry and emission characteristics, which allow researchers to create a toolbox of agents to better tailor patient care. We have identified 3,4,3-(LI-1,2-HOPO), hereafter called HOPO, as a robust chelator for radiometals for molecular imaging and radiotherapy. HOPO is an octadentate chelator that possesses four 1,2-hydroxypyridinone moieties for coordinating to radiometals through oxygen donor atoms. HOPO was originally developed as a decorporation agent for removing actinides from biological systems and is presently in clinical trials for this purpose. We first established the stabilization of the positron emitter, Zr-89, by HOPO and we prepared the bifunctional derivative, p-SCN-Bn-HOPO, that can be conjugated to antibodies. In comparison to the clinically used chelator, Desferrioxamine B (DFO), we demonstrated the successful use of ⁸⁹Zr-HOPO-trastuzumab to image BT474 breast cancer with low background, good tumor to organ contrast, and, importantly, very low bone uptake, suggesting superior stability of the ⁸⁹ZrHOPO complex. Noting that HOPO exhibits strong binding to hard +3 and +4 metal ions, we have examined the use of HOPO and HOPO derivatives as chelators for a variety of +3 and +4 radiometals for potential applications in molecular imaging and radiotherapy.