Issue 11, 2021

High denticity oxinate-linear-backbone chelating ligand for diagnostic radiometal ions [111In]In3+ and [89Zr]Zr4+

Abstract

Advances in nuclear medicine depend on chelating ligands that form highly stable and kinetically inert complexes with relevant radiometal ions for use in diagnosis or therapy. A new potentially decadentate ligand, H5decaox, was synthesised to incorporate two 8-hydroxyquinoline moieties on either end of a diethylenetriamine backbone decorated with three carboxylic acids, one at each N atom of the backbone. Metal complexation was assessed using nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS) with In3+, Zr4+ and La3+. Solution thermodynamic studies provided the stepwise protonation constants and metal formation constants, indicating a high affinity for both In3+ and Zr4+ (pIn = 32.3 and pZr = 34.7), and density functional theory (DFT) calculations provided insight into the coordination environments with either metal ion. Concentration dependent radiolabeling experiments with [111In]InCl3 and [89Zr]ZrCl4 showed promise as quantitative radiolabeling (>95%) occurred at micromolar concentrations, under mild, near-physiological conditions of pH 7 and room temperature for 30 minutes. Serum stability of both radiometal complexes was investigated and the [111In]In(decaox) complex remained 91% intact after 24 hours while the [89Zr]Zr(decaox) complex was 86% intact over the same time, comparable to other chelating ligands previously assessed with the same methods. The high radiolabeling yields, limited serum protein transchelation and structural insight of the [89Zr]Zr(decaox) complex suggest a promising fit between the oxinate-containing ligand and the Zr4+ ion, setting the stage for further investigations with a functionalised version of the chelator for its potential in PET imaging.

Graphical abstract: High denticity oxinate-linear-backbone chelating ligand for diagnostic radiometal ions [111In]In3+ and [89Zr]Zr4+

Supplementary files

Article information

Article type
Paper
Submitted
12 dec 2020
Accepted
16 feb 2021
First published
17 feb 2021

Dalton Trans., 2021,50, 3874-3886

High denticity oxinate-linear-backbone chelating ligand for diagnostic radiometal ions [111In]In3+ and [89Zr]Zr4+

L. Southcott, X. Wang, L. Wharton, H. Yang, V. Radchenko, M. Kubeil, H. Stephan, M. de Guadalupe Jaraquemada-Peláez and C. Orvig, Dalton Trans., 2021, 50, 3874 DOI: 10.1039/D0DT04230G

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements