Improving HyperCEST performance by favorable xenon exchange conditions in liposomal nanocarriers.

MRI reporters that combine signal enhancement from saturation transfer with hyperpolarized Xe show nanomolar detection sensitivity for in vitro studies. However, they need further improvement for accelerated CEST build-up that sufficiently dominates the intrinsic loss of hyperpolarization under in vivo conditions. This study introduces liposomes with a HyperCEST-active lipopeptide to enhance the efficiency of a well known Xe host, CrA-ma, with medium Xe exchange kinetics in aqueous environment, by two orders of magnitude. The depolarization time for constant saturation power but increasing saturation time is used as a comparative measure to rank different nanocarrier formulations. A variable cage load illustrates that the available CEST sites should be well distributed throughout the nanocarriers to avoid inefficiency from back exchange. For a liposome loading with only 2 mol% CrA-lipopeptide, the higher exchange kinetics allowed us to work even with 17-fold lower saturation power than for CrA-ma itself to achieve significant image contrast with Xe. Overall, this study illustrates the wide parameter space that is now available when incorporating CrA-labelled lipopeptides into liposomal carriers.