A Pharmacokinetic and MRI Study of Unilamellar Gadolinium-, Manganese-, and Iron-DTPA-Stearate Liposomes as Organ-Specific Contrast Agents

摘要

Small unilamellar liposomes that contain the lipophilic chelate DTPA-stearate (DTPASA) were used as carriers for the paramagnetic metal ions gadolinium, manganese, and iron. The iron liposomes were unstable in vitro and thus not studied further. The natural targeting properties of these liposomes to the reticuloendothelial system was used in rats and dogs for the imaging of liver and spleen. In vitro incubations with human plasma, followed by high-pressure liquid chromatography (HPLC) separation of the Gd-DTPASA and Mn-DTPASA liposomes showed that after an incubation period of 24 hours, only 4percnt; of the gadolinium was bound to the plasma proteins, whereas, with the Mn-DTPASA liposomes, a transfer of 40percnt; manganese was seen. These results indicate that the Mn-DTPASA complex is not stable. On T1-weighted images, both liposome preparations gave a strong signal enhancement of the organs of the mononuclear phagocyte system (MPS). Gadolinium liposomes accumulated in the liver of rats at a peak concentration 4 hours after application and at a higher concentration compared with the manganese liposomes. Gd-DTPASA liposomes had an elimination half-time from the liver of 61 hours. Manganese liposomes produced stronger contrast at lower concentrations and had faster elimination kinetics from the liver, with a major elimination half-time of 10 hours. Both chelate complexes were eliminated predominantly by the hepatobiliary route. Thus, liposomal Gd-DTPASA appears to be a stable, efficient, and specific magnetic resonance imaging (MRI) contrast agent for the upper abdomen.