Liposomes are spheres composed of relatively non-toxic and biodegradable lipids which are useful for entrapping a variety of drugs, decreasing drug toxicity and targeting. For a number of years we have evaluated the use of liposomes as MR contrast agents. We have prepared and tested contrast agents entrapped within the internal aqueous space of liposomes as well as liposomes incorporating lipophilic contrast agents in the lipid bilayer. When chelates such as Gd-DTPA are entrapped within the internal aqueous space of lipid vesicles, delivery is primarily to the Kupffer cells and clearance is slow. Manganese ions entrapped within lipid vesicles cause more enhancement per micromole of paramagnetic ion than gadolinium. Lipophilic derivatives of manganese EDTA chelates when incorporated into liposomes confer the greatest hepatic enhancement per micromole of metal ion and have favorable clearance kinetics. An apparently hepatocyte specific liposomal MR contrast agent has been prepared based upon a lipophilic derivative of manganese EDTA, which enhances the liver and increases liver/tumor contrast to noise more than most other contrast agents per micromole of metal ion. The agent has very high relaxivity, Rl over 30 and R2 over 40 per micromole of manganese. Cardiac imaging shows pronounced blood pool enhancement with potential for myocardial perfusion imaging. Membrane bound lipophilic paramagnetic chelates hold promise as improved liposomal contrast agents for MR.
ASJC Scopus subject areas
- Pharmaceutical Science