Small, Fluorinated Mn2+ Chelate as an Efficient 1H and 19F MRI Probe

Author:

Garda Zoltán12ORCID,Szeremeta Frédéric1,Quin Océane1,Molnár Enikő2,Váradi Balázs2,Clémençon Rudy1,Même Sandra1,Pichon Chantal134,Tircsó Gyula2ORCID,Tóth Éva1ORCID

Affiliation:

1. Centre de Biophysique Moléculaire CNRS UPR 4301 Université d'Orléans rue Charles Sadron 45071 Orléans France

2. Department of Physical Chemistry University of Debrecen Egyetem tér 1 4010 Debrecen Hungary

3. Inserm UMS 55 ART ARNm and LI2RSO University of Orléans F-45100 Orléans France

4. Institut Universitaire de France 1 rue Descartes F-75035 Paris France

Abstract

AbstractWe explore the potential of fluorine‐containing small Mn2+ chelates as alternatives to perfluorinated nanoparticles, widely used as 19F MRI probes. In MnL1, the cyclohexanediamine skeleton and two piperidine rings, involving each a metal‐coordinating amide group and an appended CF3 moiety, provide high rigidity to the complex. This allows for good control of the Mn−F distance (rMnF=8.2±0.2 Å determined from 19F relaxation data), as well as for high kinetic inertness (a dissociation half‐life of 1285 h is estimated for physiological conditions). The paramagnetic Mn2+ leads to a ~150‐fold acceleration of the longitudinal 19F relaxation, with moderate line‐broadening effect, resulting in T2/T1 ratios of 0.8 (9.4 T). Owing to its inner sphere water molecule, MnL1 is a good 1H relaxation agent as well (r1=5.36 mM−1 s−1 at 298 K, 20 MHz). MnL1 could be readily visualized in 19F MRI by using fast acquisition techniques, both in phantom images and living mice following intramuscular injection, with remarkable signal‐to‐noise ratios and short acquisition times. While applications in targeted imaging or cell therapy monitoring require further optimisation of the molecular structure, these results argue for the potential of such small, monohydrated and fluorinated Mn2+ complexes for combined 19F and 1H MRI detection.

Publisher

Wiley

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