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Unprecedented Kinetic Inertness for a Mn2+ -Bispidine Chelate: A Novel Structural Entry for Mn2+ -Based Imaging
Daouda Ndiaye1, Maryame Sy2, Agnès Pallier1
1Centre de Biophyisique Moléculaire, CNRS UPR 4301, Université d'Orléans, rue Charles Sadron, 45071, Orléans, France.
Abstract:
The search for more biocompatible alternatives to Gd3+ -based MRI agents, and the interest in 52 Mn for PET imaging call for ligands that form inert Mn2+ chelates. Given the labile nature of Mn2+ , high inertness is challenging to achieve. The strongly preorganized structure of the 2,4-pyridyl-disubstituted bispidol ligand L1 endows its Mn2+ complex with exceptional kinetic inertness. Indeed, MnL1 did not show any dissociation for 140 days in the presence of 50 equiv. of Zn2+ (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 Mn2+ 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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