Transferrin promotion of 67Ga and 59Fe uptake by cultured mouse myeloma cells.

Radiotracer 67Ga-citrate is used as a tumor-seeking agent in clinical imaging investigations although fundamental reasons for its high uptake in certain malignant lesions remain unexplained. The mechanism by which 67Ga becomes concentrated in tumor cells has been investigated by comparing 67Ga and 59Fe uptake by cultured mouse myeloma cells with particular reference to uptake stimulation by transferrin. Concentrations of human transferrin down to 2 microgram/ml greatly stimulated cellular uptake of both tracers, whereas bovine transferrin proved relatively inactive. The rates of stimulated uptake of both tracers were similar as was their high degree of retention by cells, but their quantitative dependencies on transferrin concentration showed characteristic differences. Pretreatment of human transferrin with saturating amounts of nonradioactive Fe3+ canceled its ability to promote 59Fe uptake, but it had little effect on its promotion of 67Ga uptake. Further increase in the amount of added Fe3+ did cause a progressive depression of 67Ga uptake, but this effect probably relates to the iron distribution in the whole-cell culture system including the fetal calf serum component of cell growth medium. The results suggest that 67Ga and 59Fe reveal different aspects of the interaction of transferrin with cells.