A simple and efficient method for radiolabeling of preformed liposomes.

A simple and efficient method for radiolabeling preformed liposomes was developed using hepatobiliary imaging agent (99m)Tc-diisopropyl iminodiacetic acid ((99m)Tc-DISIDA). Chloroform extraction of (99m)Tc-DISIDA from aqueous solutions results in 80% radioactivity in the organic phase due to its lipophilic properties. However, with the presence of reduced glutathione (gamma-Glu-Cys-Gly), chloroform extraction results in only 30% of label in the organic phase because the (99m)Tc-DISIDA complex undergoes reduction decomposition to more hydrophilic species by reaction with glutathione. The incorporation efficiency of the (99m)Tc-DISIDA into the liposomes containing reduced glutathione was greater than 90%. The labeled liposomes were stable up to 24 h in saline and 90% FBS after preparation. Biodistribution studies in mice showed that (99m)Tc labeled liposomes accumulated in liver and spleen at 24 h postinjection, unlike (99m)Tc-DISIDA. Compared to hexamethylpropyleneamine oxime (HMPAO), the (99m)Tc-DISIDA compound is much cheaper and has a longer shelf life when used for liposome labeling. The labeling technique described here could be used for monitoring pharmacokinetic and pharmacodynamic changes of liposomes, and tumor or infection imaging when coupled with targeting antibodies.