R3-Noria-methanesulfonate: A Molecular Cage with Superior Hyperpolarized Xenon-129 MRI Contrast

Hyperpolarized (HP) xenon-129 (¹²⁹Xe) magnetic resonance imaging (MRI) has the potential to be used as a molecular imaging modality. For this purpose, numerous supramolecular cages have been developed and evaluated in the past. Herein, we report a novel and unique macrocycle that can be successfully utilized for xenon MRI, the resorcinarene trimer methanesulfonate (R3-Noria-MeSO₃H). This molecule is capable of two different contrast mechanisms for xenon-MRI, resulting from an increase in the effective spin–spin relaxation and hyperpolarized chemical exchange saturation transfer (HyperCEST). We have demonstrated a superior negative contrast caused by R3-Noria-MeSO₃H on HP ¹²⁹Xe MRI at 3.0 T as well as HyperCEST imaging of the studied macrocycle. Additionally, we have found that the complex aggregation behaviors of R3-Noria-methanesulfonate and its impact on xenon-129 relaxivity are an area for future study.