CYCLODEXTRINS: AN APPROPRIATE SCAFFOLD FOR NEW MRI THERANOSTIC PROBES

Géraldine Gouhier

University of Rouen, UMR CNRS 6014 COBRA, France

Abstract

Thanks to its high resolution and despite its low sensitivity, MRI is widely used for human noninvasive imaging. In order to significantly improve the sensitivity of this technique to visualize deep anatomic tissues, the design of new contrast agents remains a challenging research area. The most commonly contrast agents used at clinical level enhance the relaxivity of the protons of water molecules coordinated to the gadolinium thus producing a single and no specific MRI signal. Our aim is to synthesize new smart molecular MRI contrast agents with higher relaxivities in order to increase the detection threshold and to visualize in vivo drug vectorization.

We developed new biologically switchable smart contrast agents based on cyclodextrins scaffolds. Gadolinium(III) was coordinated to various ligands introduced on the primary side of β-cyclodextrin. A suitably functionalized spacer was grafted on its secondary side as a future support of a drug moiety (Scheme 1). After biological recognition, a specific peptide could be cleaved releasing the drug on the site of interest.

Scheme 1. Theranostic approach - A new smart MRI probe.

As preliminary studies we proved that the formation of inter and intramolecular inclusion complexes with the internal cavity of the cyclodextrin enhanced significantly the MRI signal by disturbance of the hydration spheres of gadolinium. Relaxometry and in vivo studies on mice’s cardiac area will be reported.

This strategy can be applied to reach personalized, earlier and more accurate theranostic markers.

G. Gouhier, F. Estour, WO Patent 2010/070126 A2, 2010. I. Zgani, H. Idriss, C. Barbot, F. Djedaïni-Pilard, S. Petit, M. Hubert-Roux, F. Estour, G. Gouhier Org. Biomol. Chem., 2017, 15, 564-569.

Keywords: Relaxometry, cyclodextrin, theranostic, complexes, gadolinium