Unprecedented Kinetic Inertness for a Mn -Bispidine Chelate: A Novel Structural Entry for Mn -Based Imaging Agents.
Fiche publication
Date publication
juillet 2020
Journal
Angewandte Chemie (International ed. in English)
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CHARBONNIERE Loïc
Tous les auteurs :
Ndiaye D, Sy M, Pallier A, Même S, de Silva I, Lacerda S, Nonat AM, Charbonnière LJ, Tóth É
Lien Pubmed
Résumé
The search for more biocompatible alternatives to Gd -based MRI agents, and the interest in Mn for PET imaging call for ligands that form inert Mn chelates. Given the labile nature of Mn , high inertness is challenging to achieve. The strongly preorganized structure of the 2,4-pyridyl-disubstituted bispidol ligand L endows its Mn complex with exceptional kinetic inertness. Indeed, MnL did not show any dissociation for 140 days in the presence of 50 equiv. of Zn (37 °C, pH 6), while recently reported potential MRI agents MnPyC3A and MnPC2A-EA have dissociation half-lives of 0.285 h and 54.4 h under similar conditions. In addition, the relaxivity of MnL (4.28 mm s at 25 °C, 20 MHz) is remarkable for a monohydrated, small Mn chelate. In vivo MRI experiments in mice and determination of the tissue Mn content evidence rapid renal clearance of MnL . Additionally, L could be radiolabeled with Mn and the complex revealed good stability in biological media.
Mots clés
52Mn, MRI, contrast agents, kinetic inertness, manganese
Référence
Angew. Chem. Int. Ed. Engl.. 2020 Jul 13;59(29):11958-11963