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Xenon MRI: all of the probes that you want

CEA Teams from the CEA-iBiTec-S and the CEA-Iramis have developed a technique to rapidly make large quantities of probes for xenon MRI. These specific probes are able to target a desired molecule to be observed, such as a protein involved in a particular disease. This on-demand functionalization, using “click chemistry” based on cryptophane, opens new perspectives for high-precision MRI imaging.

Published on 14 August 2013

Conventional magnetic resonance imaging (MRI) uses the magnetic properties of protons contained within the hydrogen atoms of the organism. This non-invasive technique is certainly powerful, although it lacks sensitivity for studies at the molecular level. Xenon MRI is a promising approach to increase sensitivity and therefore the accuracy of the images. Unlike conventional MRI, which detects the organism’s protons, this technique uses the exogenous and harmless xenon atom, whose magnetic resonance signal can be greatly amplified through hyperpolarization techniques. However, xenon is “blind” in its native state; the idea of the researchers is thus to make small systems enabling xenon to recognize its biological targets.

The scientists are working on caged molecules, in which xenon is encapsulated, to easily navigate within the body. The currently proposed molecules are constructed around a core of cryptophane; this cage-like macromolecule is commonly synthesized to encapsulate all sorts of compounds of interest. However, their drawback is their lack of solubility in water, which is an obstacle to their use in a biological context.

To remedy this and allow xenon to recognize its targets, the researchers designed and synthesized a new cryptophane with two innovative features. First of all, it is water soluble due to the addition of a group of polyethylene glycol chains (PEGylation), resulting in good solubility and diffusion through the body. Furthermore, it is equipped with alkyne groups (CnH2n-2) for an easy functionalization by “click chemistry”. Preliminary tests have shown the effectiveness of this new cryptophane compound, as well as it safety at experimental imaging concentrations. It will be tested during in vivo imaging experiments in small animal models.
Representation of xenon MRI probes with pegylation (PEG) groups.    

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