Enhancement of the Cell Specific Proton Relaxivities of Human Red Blood Cells via Loading With Gadoteric Acid

Human red blood cells were loaded with gadoteric acid by two different methods. The methods comprised either hypo-osmolar incubation or a hypo-osmolar pulse in the presence of gadoteric acid. The resulting enhancements in proton relaxivities of cell suspensions in 1.4 T were measured and the effect of incubation osmolarity on the resulting proton relaxivity was also studied. The osmotic pulse method was found to yield the greatest cell-specific relaxivity enhancements (71-fold for longitudinal relaxivity and 39-fold for transverse relaxivity). The spatial distribution of the gadolinium within the cells was studied using energy filtered transmission electron microscopy to generate gadolinium M-edge jump ratio images. All surviving cells exposed to gadoteric acid under hypo-osmolar conditions showed enhanced (relative to control cells) and generally uniform intensity within the cells in gadolinium jump ratio images suggesting all cells are susceptible to loading and that the loading is generally spatially uniform within each cell. There was some evidence for a small amount precipitation or aggregation of gadolinium within some cells prepared by the hypo-osmolar incubation method.