LABELING OF PREFORMED LIPOSOMES WITH GA-67 AND TC-99M BY CHELATION

Abstract

A long-chain hydrocarbon covalently coupled to diethylenetriaminepentaacetic acid (stearylamine-DTPA) was synthesized and incorporated in liposomes during their preparation. The lipophilic hydrocarbon chain anchors the molecule in the lipid bilayer, exposing the DTPA groups on the surface for chelation. Ethanolic solutions of the lipids are evaporated to dryness under N in multidose vials; the lipids are suspended in the vial by adding a small volume of distilled water followed by sonication. The liposomes are then labeled by transcomplexation in the case of 67Ga and by conventional stannous reduction in the case of 99mTc, by adding the activities directly to the vial. These liposomes bind 95 .+-. 5% of 67Ga and 99mTc activity, as determined by paper chromatograph assay, eliminating the need for a purification step. The labeled liposomes release .apprx. 5% of their 67Ga activity, and .apprx. 30% of their 99mTc activity after 2 h of incubation in 50% human plasma at 37.degree. C. Activity released from liposomes labeled with 67Ga or 99mTc oxine is much greater under the same conditions. In normal mice the labeled liposomes show biodistributions that are comparable with that obtained with liposomes labeled by conventional techniques.