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Uptake of Gallium-67 by Human Leukemic Cells: Demonstration of Transferrin Receptor-dependent and Transferrin-independent Mechanisms¹

Section of Hematology/Oncology, Department of Medicine, The Medical College of Wisconsin, Milwaukee, Wisconsin 53226

We have studied the role of transferrin and the transferrin receptor in the uptake of ⁶⁷Ga by the human leukemic cell line HL60. In the absence of transferrin, HL60 cells incorporated about 1% of the ⁶⁷Ga dose over 6 h. The presence of transferrin increased cellular ⁶⁷Ga uptake approximately 10-fold. Transferrin-mediated uptake of ⁶⁷Ga was blocked by an anti-transferrin receptor monoclonal antibody, and decreases in the density of cellular transferrin receptors led to corresponding decreases in the transferrin-dependent uptake of ⁶⁷Ga. Changes in the cellular ferritin content did not significantly influence the uptake of ⁶⁷Ga by either transferrin-independent or transferrin-dependent pathways. Regardless of the mechanism of uptake, a significant amount of intracellular ⁶⁷Ga was found to be associated with immunoprecipitable ferritin as well as with a free pool. This free intracellular ⁶⁷Ga appeared to be kinetically active since cells released ⁶⁷Ga back to the media over time. Our results demonstrate the existence of a dual mechanism for the cellular uptake of ⁶⁷Ga and suggest that the preferential uptake of ⁶⁷Ga by lymphomas is related to the high density of transferrin receptors known to be expressed by these tumors in vivo.

¹ Supported by New Investigator Research Grant CA 41740-01 from the National Cancer Institute to C. R. C.

² To whom requests for reprints should be addressed.

Received 12/29/86. Revised 4/13/87. Accepted 5/ 1/87.

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