Gallium-67 transport across artificial biological membranes.

Abstract

Abstract The influence of composition of model artificial membranes on the incorporation of 67Ga-citrate and 67Ga-transferrin complexes has been investigated using an ultracentrifugation method to obtain levels of uptake. 67Ga-citrate was taken up to the extent of 12% in neutral phosphatidylcholine or phosphatidylcholine:cholesterol membranes and positively-charged phosphatidylcholine:stearylamine membranes but near 100% in phosphatidylcholine systems containing either dicetylphosphate or cholesterol and dicetylphosphate in combination. 67Ga-transferrin was incorporated to the extent of 35% in neutral and 3-component negatively-charged membranes, 70% in positively-charged membranes, and 94% in 2-component negatively-charged membranes. Calculations indicated that most of the activity incorporated is associated with the lipid phase. Varying the ratios of membrane components yielded results of maximum incorporation of 67Ga-citrate which were consistent with high concentrations of dicetylphosphate and optimum concentrations of cholesterol which were below 33 mol%. Cholesterol improved the ability of positively-charged membranes to take up 67Ga-citrate but this was somewhat dependent on the concentration of phosphatidylcholine. The results are interpreted using a physical-chemical approach. 67Gacitrate and 67Ga-transferrin have an apparent affinity to negatively-charged sites within or on the surface of the membrane but the ability for partitioning also plays a prominent role. In the case of 67Ga-transferrin, the protein presumably extends through the bilayer and, therefore, is little affected by modifications of phospholipid molecular size. On the other hand, 67Ga-citrate partitions only under certain circumstances, but when this occurs its level of uptake is influenced by the characteristics of the lipid environment.