Mechanism of radiogallium localization in tumors: role of iron-binding proteins, transferrin and lactoferrin

Lactoferrin, an intracellular iron binding protein which has a high affinity for Gallium was used as a probe to evaluate the effect of protein binding on Ga uptake. In nude mice bearing human malignant mesothelioma, both transferrin and lactoferrin reduced the tumor uptake of gallium. Tumor uptake of Gallium was markedly decreased following Ga-LF compared to Ga-TF. With lactoferrin, more gallium was taken up by liver compared to transferrin. In an in vitro tumor model the effect of transferrin and lactoferrin on the cell binding of Ga-67 and Fe-59 was studied. Both proteins promoted gallium binding to cells; optimal concentration is 160μg/ml. Lactoferrin enhancement of gallium binding to cells was much higher than transferrin. Binding of Fe-59 to the cells was inhibited in the presence of proteins. Under similar conditions binding of I-125-lactoferrin was greater than I-125-transferrin. These discrepant results do not clarify the mechanism of cell uptake of gallium. Areas for further investigation are identified