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

An approach for hyperpolarized (129) Xe molecular sensors is explored using paramagnetic relaxation agents that can be deactivated upon chemical or enzymatic reaction with an analyte. Cryptophane encapsulated (129) Xe within the vicinity of the paramagnetic center experiences fast relaxation that, through chemical exchange of xenon atoms between cage and solvent pool, causes accelerated hyperpolarized (129) Xe signal decay in the dissolved phase. In this proof-of-concept work, the relaxivity of Gadolinium(III) -DOTA on (129) Xe in the solvent was increased eightfold through tethering of the paramagnetic molecule to a cryptophane cage. This potent relaxation agent can be 'turned off' specifically for (129) Xe through chemical reactions that spatially separate the Gd(III) centre from the attached cryptophane cage. Unlike (129) Xe chemical shift based sensors, the new concept does not require high spectral resolution and may lead to a new generation of responsive contrast agents for molecular MRI.