Liposomes as MR contrast agents: Pros and cons

Liposomes are generally thought of as being useful for entrapping drugs within their internal aqueous space. When used with MR contrast agents, this has the drawback that water flux across the membrance bilayer is limiting to contrast enhancement. This can be partially overcome by making the liposomes very small, such that surface area is relatively great compared to internal volume, thereby facilitating water exchange. Alternatively the membranes can be designed to be permeable to water but this may render the vesicles unstable in serum. Another approach is to incorporate the contrast agents into the lipid bilayer. By designing novel complexes of manganese with the ligands incorporated onto dual acyl chains, we have achieved R1 and R2 values of over 20/mmol sec⁻¹ or more than five times higher than Gd‐DTPA. Hepatic metastasis detection is significantly improved in rats at doses of only 10 μmol/kg manganese. Membrane‐bound manganese complexes function as highly effective liver imaging agents and merit further study for development as agents to undergo human clinical trials. © 1991 Academic Press, Inc.