NMR and ESR study of liposome delivery of Mn2+ to murine liver.

The mechanism of tissue relaxation of liposome-delivered Mn2+ as a contrast agent for magnetic resonance imaging (MRI) was examined using magnetic resonance and electron spin resonance (ESR) techniques. It is known that liposomes of the size and composition used in this study are taken up by fixed liver macrophages (Kupffer cells). It was determined that Mn2+ must be released from the liposomes in order to affect the water proton relaxation rate in the liver. As long as the Mn2+ was confined to the Kupffer cells, no substantial changes in the relaxation of the majority of the liver water were observed. Unlike other contrast agents delivered to the Kupffer cells (for example, Gd-starch microspheres or magnetite), once the Mn2+ is delivered and released into the Kupffer cells, it can diffuse from the Kupffer cells and be rapidly taken up by the hepatocytes. This seems to be the mechanism for selective relaxation enhancement in the liver. A consequence of this behavior is that the time at which maximum contrast enhancement occurs for MRI can be varied by the choice of liposome phospholipid composition. ESR techniques were used to directly determine the state of Mn2+ and the integrity of liposomes in various stages of processing.