Molecular Sensing with Hyperpolarized (129) Xe Using Switchable Chemical Exchange Relaxation Transfer

Area of Science:

• Magnetic Resonance Imaging
• Chemical Sensors
• Xenon-129 Spectroscopy

Background:

• Hyperpolarized (129)Xe is a sensitive probe for molecular imaging.
• Paramagnetic relaxation agents (PRAs) can enhance MRI signal but require specific designs for analyte-responsive sensing.
• Current (129)Xe sensors often rely on chemical shift changes, demanding high spectral resolution.

Purpose of the Study:

• To explore a new concept for hyperpolarized (129)Xe molecular sensors using switchable PRAs.
• To demonstrate proof-of-concept for a sensor where the relaxation agent can be deactivated upon reaction with an analyte.
• To investigate the potential for developing responsive contrast agents for molecular MRI.

Main Methods:

• Tethering a Gadolinium(III)-DOTA paramagnetic molecule to a cryptophane cage encapsulating (129)Xe.
• Measuring the effect of the tethered PRA on (129)Xe relaxation rates in the dissolved phase.
• Investigating chemical reactions to spatially separate the Gd(III) center from the cryptophane cage to deactivate relaxation.

Main Results:

• An eightfold increase in (129)Xe relaxivity was achieved by tethering Gd(III)-DOTA to a cryptophane cage.
• The tethered relaxation agent effectively accelerated (129)Xe signal decay through chemical exchange.
• A chemical reaction was demonstrated to spatially separate the Gd(III) center, effectively 'turning off' the relaxation agent for (129)Xe.

Conclusions:

• A novel approach for hyperpolarized (129)Xe molecular sensors utilizing switchable PRAs has been successfully demonstrated.
• This method offers an alternative to chemical shift-based sensors, potentially simplifying detection requirements.
• The developed concept may pave the way for a new generation of responsive contrast agents for molecular MRI.