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 ^99mTc-"SNS/S" complexes is introduced. This labeling method can be applied to liposome radiolabeling with not only ^99mTc but also two therapeutic radionuclides, ¹⁸⁶Re and ¹⁸⁸Re. Liposomes encapsulating glutathione (GSH) were studied for ^99mTc 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 ^99mTc-"BMEDA", ^99mTc-"BMEDA + BT", ^99mTc-"BMBuA", and ^99mTc-"BMBuA + BT", for liposome labeling. The labeling efficiencies of ^99mTc-GSH liposomes were from 36.9 to 69.2%. After incubation in serum, ^99mTc-GSH liposomes labeled with ^99mTc-"BMEDA" or ^99mTc-"BMEDA + BT" had the best labeling stability of the formulations tested. Distribution studies after intravenous injection of ^99mTc-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 ¹⁸⁶Re or ¹⁸⁸Re labeled liposomes and for diagnostic imaging.