Labeling of preformed liposomes with Ga-67 and Tc-99m by chelation.

We have synthesized a long-chain hydrocarbon covalently coupled to diethylene-triaminepenta-acetic acid (stearylamine-DTPA) and have incorporated this compound 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 nitrogen 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 Ga-67 and by conventional stannous reduction in the case of Tc-99m, by adding the activities directly to the vial. These liposomes bind 95 +/- 5% of Ga-67 and Tc-99m activity, as determined by paper chromatograph assay, eliminating the need for a purification step. The labeled liposomes release about 5% of their Ga-67 activity, and about 30% of their Tc-99m activity after 2 hr of incubation in 50% human plasma at 37 degrees C. Activity released from liposomes labeled with Ga-67 or Tc-99m 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.