Frequency-encoded MRI-CEST agents based on paramagnetic liposomes/RBC aggregates

Paramagnetic liposomes containing Dy-HPDO3A in their inner water compartment and carrying a residual positive charge on their outer surface have been electrostatically bound to the membrane of red blood cells (RBCs). These aggregates yield two chemical exchange saturation transfer (CEST) pools represented by liposomal water protons (LipoCEST) and cytoplasmatic water protons (ErythroCEST), respectively. The absorption frequencies of the two pools fall at the negative and positive side of the solvent water resonance as expected from the dipolar (LipoCEST) and BMS (bulk magnetic susceptibility) (ErythroCEST) origin of the paramagnetic induced shift of their water protons resonances, respectively. In vivo magnetic resonance imaging (MRI) shows that the liposomes/RBC aggregates report about the vascular volume whereas the residual LipoCEST effect informs about the presence of released liposomes in the region of interest (ROI). Besides being an innovative blood cell labeling for MRI, the LipoCEST/RBC aggregates provide a route to improve the circulation lifetime of the liposomes and the CEST procedure allows assessing the deassembly of the aggregates and accumulation of the liposomes in the ROI.