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Role of the Acidic Receptosome in the Uptake and Retention of ⁶⁷Ga by Human Leukemic HL60 Cells¹

Division of Hematology-Oncology, Department of Medicine, The Medical College of Wisconsin, Milwaukee, Wisconsin 53226

The uptake of ⁶⁷Ga by HL60 cells requires binding of ⁶⁷Ga-transferrin (Tf) to cell surface Tf receptors. To further examine this process, we have studied early events in the cellular uptake of ⁶⁷GaTf. Cell surface-bound ⁶⁷GaTf and ⁵⁹FeTf displayed similar kinetics during the first 10 min of uptake. Thereafter, approximately 10% of intracellular ⁶⁷Ga was released by cells while ⁵⁹Fe internalization continued to increase with time. In pulse-chase studies of ¹²⁵I-Tf-⁶⁷Ga uptake, internalized ¹²⁵I-Tf, but not ⁶⁷Ga, was chased out of cells by nonradioactive Tf-Ga. Exposure of cells to monensin, a carboxylic ionophore, during initial uptake decreased the internalization of both ¹²⁵I-Tf and ⁶⁷Ga. Exposure to monensin at a later time, after cells had incorporated ¹²⁵I-Tf-⁶⁷Ga or ⁵⁹FeTf, caused an increase in the release of ⁶⁷Ga and ⁵⁹Fe with a decrease in the release of ¹²⁵I-Tf. Ammonium chloride inhibited the internalization of both ⁶⁷Ga and ⁵⁹Fe. ⁶⁷GaTf uptake by HL60 cells involves initial internalization into an acidic receptosome. This is followed by dissociation of ⁶⁷Ga and Tf and subsequent trafficking of each to separate intracellular compartments. Disruption of this process by monensin results in the release of ⁶⁷Ga from cells.

¹ This work was supported by USPHS Grant RO1 CA41740 from the National Cancer Institute to C. R. C.

² To whom requests for reprints should be addressed, at Division of Hematology/Oncology, Medical College of Wisconsin, 8700 W. Wisconsin Avenue, Milwaukee, WI 53226.

Received 8/ 1/89. Revised 11/ 2/89. Accepted 11/27/89.

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