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Transferrin Promotion of ⁶⁷Ga and ⁵⁹Fe Uptake by Cultured Mouse Myeloma Cells¹

The Walter and Eliza Hall Institute of Medical Research [A. W. H.], and The Cancer Institute [R. G. S.], Melbourne, Australia 3000

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 µg/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.

¹ This research was supported in part by the National Health and Medical Research Council of Australia and the Wellcome Trust, England.

² To whom requests for reprints should be addressed, at The Cancer Institute, 481 Little Lonsdale Street, Melbourne, Australia 3000.

Received 2/ 1/77. Accepted 7/ 6/77.

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