A novel liposome radiolabeling method using 99mTc-"SNS/S" complexes:: In vitro and in vivo evaluation

Liposomes are important carriers for controlled drug release, for gene or antisense therapy, and for immunization. Radiolabeled liposomes can be used to evaluate the in vivo behavior of different liposome formulations, as well as for diagnostic imaging and radionuclide therapy. A novel method for radiolabeling liposomes with Tc-99m-"SNS/S" complexes is introduced. This labeling method can be applied to liposome radiolabeling with not only Tc-99m but also two therapeutic radionuclides, Re-186 and Re-188. Liposomes encapsulating glutathione (GSH) were studied for Tc-99m labeling. N,N-bis(2-mercaptoethyl)-N',N'-diethyl-ethylenediamine (BMEDA), N,N-bis(2-mercaptoethyl)-1-butylamine (BMBuA), and benzene thiol (BT) were investigated to make Tc-99m-"BMEDA", Tc-99m-"BMEDA + BT", Tc-99m-"BMBuA", and Tc-99m-"BMBuA + BT", for liposome labeling. The labeling efficiencies of Tc-99m-GSH liposomes were from 36.9 to 69.2%. After incubation in serum, Tc-99m-GSH liposomes labeled with Tc-99m-"BMEDA" or Tc-99m-"BMEDA + BT" had the best labeling stability of the formulations tested. Distribution studies after intravenous injection of Tc-99m-liposomes composed of distearoyl phosphatidylcholine (DSPC) and cholesterol had a slow blood clearance and a high spleen accumulation demonstrating the in vivo labeling stability of the radiolabeled liposomes. The 99mTc-liposomes have great potential as a radiopharmaceutical system for evaluating various kinds of liposomes with different lipid composition, for evaluating in advance a subsequent radionuclide therapy using Re-186 or Re-188 labeled liposomes and for diagnostic imaging. (C) 2003 Wiley-Liss, Inc. and the American Pharmacists Association.