Unprecedented kinetic inertness for a Mn2+‐bispidine chelate: a novel structural entry for Mn2+‐based imaging agents
Résumé
The search for more biocompatible alternatives to Gd 3+-based MRI agents, and the interest in 52 Mn for PET imaging call for ligands that form inert Mn 2+ chelates. Given the labile nature of Mn 2+ , high inertness is challenging to achieve. The strongly preorganized structure of the 2,4-pyridyl-disubstituted bispidol ligand L1 endows its Mn 2+ complex with exceptional kinetic inertness. Indeed, MnL1 did not show any dissociation for 140 days in the presence of 50 eq. of Zn 2+ (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 MnL1 (4.28 mM-1 s-1 at 25°C, 20 MHz) is remarkable for a monohydrated, small Mn 2+ chelate. In vivo MRI experiments in mice and determination of the tissue Mn content evidence rapid renal clearance of MnL1. Additionally, L1 could be radiolabeled with 52 Mn and the complex revealed good stability in biological media.
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