CE07 - Chimie moléculaire

Selective Cu(II) detection by MRI: Gd-based contrast agents linked to bioadapted Cu chelatorsnding units – SteRIc

Submission summary

The goal of this project is to develop MRI-based sensors for selective copper(II) detection, designed in order to be applicable in relevant biological samples in particular blood serum. Imaging Cu with a tridimensional and functional imaging modality such as magnetic resonance imaging (MRI) will help to better understand Cu homeostasis, i.e. the mechanisms of extracellular Cu distribution, uptake and trafficking. It is particularly relevant for diseases characterized by excess and/or misplaced copper, such as Wilson’s and Alzheimer’s diseases.
Cation-responsive MRI contrast agents (CA) are typically composed of three parts: (1) A cation-binding unit which must be selective to the cation to sense, (2) a gadolinium(III) complex, which is the MRI active part and (3) a linker between the two units. If Zn-responsive CA have successfully passed to in vivo studies, Cu detection is still in its infancy held back by selectivity and sensitivity issues.
We propose here to use original Cu(II)-binding units, completely different to what has been previously proposed in the literature and that (a) are specific for Cu(II) over the other metal ions, (b) have appropriate Cu(II) affinity to detect low Cu(II) concentrations without perturbing the local Cu(II) presence and (c) will be optimized for the highest relaxivity response to Cu(II). The full characterisation of the systems in the presence or absence of Cu will allow for an optimised design of the CA and ultimately the highest response with Cu, which will ensure a sensitive detection. The most relevant complexes will be tested in vitro on blood samples.
The success of this project relies on the complementarity of the teams involved which are specialised in Cu complexation, and design and characterisation of MRI contrast agents.

Project coordination

Angélique Sour (Institut de Chimie de Strasbourg)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

CBM Centre national de la recherche scientifique
IC Institut de Chimie de Strasbourg

Help of the ANR 357,645 euros
Beginning and duration of the scientific project: March 2023 - 42 Months

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