An improved method for the preparation of liposomal gadolinium-DTPA. Ionophore-mediated active entrapment of gadolinium.

We have developed an improved method for the production of liposomal gadolinium-DTPA (Gd-DTPA). The ionophore A23187 facilitates the uptake of externally added Gd into the interior aqueous space of a unilamellar lipid vesicle, where it is chelated by passively entrapped DTPA to form the Gd-DTPA chelate in situ. The presence of a pH gradient across the vesicle membrane is not essential for Gd uptake, the extent of which apparently is limited only by the interior concentration of the chelator. Once formed internally, the Gd-DTPA complex is retained within the vesicles for at least several days at room temperature. Biodistribution studies in mice indicate that liposomal Gd-DTPA prepared by this ionophoretic loading procedure exhibits biodistribution and clearance characteristics similar to 153Gd-DTPA-labeled liposomes prepared by means of passive entrapment of the preformed chelate.