Molecular Sensing with Hyperpolarized 129Xe using Switchable Chemical Exchange Relaxation Transfer.

Aim: A new approach for hyperpolarized (hp) ¹²⁹Xe molecular sensors is explored using paramagnetic relaxation agents that can be deactivated upon chemical or enzymatic reaction with an analyte. The goal is to generate molecular MRI contrast that does not rely on small chemical shift differences. Instead, the concept seeks a switchable depolarization agent for hp ¹²⁹Xe.

Methods: Cryptophane encapsulated ¹²⁹Xe 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 ¹²⁹Xe signal decay in the dissolved phase.

Results: In this work, the relaxivity of GadoliniumIII-DOTA on ¹²⁹Xe 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 ¹²⁹Xe through chemical reactions that spatially separate the GdIII centre from the attached cryptophane cage.

Conclusions: The proof of concept study demonstrated the viability of this novel approach. Unlike ¹²⁹Xe 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.

Figure 1.: GdDOTA is a weak relaxation agent for ¹²⁹Xe. B) Cryptophane-A tethered to GdDOTA serves as a strong relaxation agent that causes fast hp ¹²⁹Xe and can be turned into a responsive relaxation agent for molecular MRI.