Cholesterol enhances the delivery of liposome-encapsulated gallium-67 to tumors

The effect of incorporation of cholesterol (CH) into liposome membranes on the delivery of 67Ga encapsulated in liposomes to tumors was studied. The changes of the blood clearance of liposomes, liposome stability in serum and liposome uptake by the liver and spleen were also examined. Liposomes were prepared from distearoylphosphatidylcholine with various amounts of CH. It became clear that large amounts of CH (above 33 mol%) dramatically enhanced liposomal delivery of 67Ga to sarcoma 180 solid tumor in mice. Large amounts of CH increased the liposome stability in serum and decreased liposome uptake by the liver and spleen after intravenous injection, thus prolonging the blood clearance of liposomes. These observations suggested that the large delivery of 67Ga by CH-rich liposomes resulted from the extended retention and increased amount of liposomes in the circulation, caused by the incorporation of large amounts of CH. Small amounts of CH decreased liposome stability and hastened blood clearance, but had little effect on 67Ga delivery to the tumor. CH-rich liposomes showed high tumor uptake, with high tumor to blood and tumor to tissue ratios of 67Ga. It is anticipated that 67Ga-carrying liposomes will be an excellent tumor imaging agent for clinical use, provided that a correct choice of CH content is made. (orig.)