Liposomal Gd-DTPA: preparation and characterization of relaxivity

Gadolinium diethylenetriamine-pentaacetic acid (DTPA) has not proved particularly useful for hepatosplenic magnetic resonance imaging. However, by entrapping the Gd-DTPA within lipid vesicles, one may exploit the ability of the reticuloendothelial system to endocytose particulates, permitting passive delivery of contrast agent to the liver and spleen while decreasing the rate of clearance of Gd-DTPA from the vasculature. Liposomes of 70-400 nm diameter containing Gd-DTPA were prepared by a freeze-thaw extrusion process. These exhibited high trapping efficiencies and excellent stability during storage. For all sizes of liposomes, the relaxivity of the entrapped Gd-DTPA was less than that of free Gd-DTPA. Relaxivity varied linearly with the surface-area-to-volume ratio of the liposomes; the smaller the liposomes, the greater the relaxivity. Liposomes containing cholesterol had a lower relaxivity than liposomes without cholesterol. The authors suggest this reflects the decrease in the water permeability coefficient caused by the presence of cholesterol in the liposome membrane.