Transferrin receptors and gallium-67 uptake in vitro

The relationship was studied between the number of transferrin-receptor positive cells and in vitro uptake of 67Ga and 125I-labeled transferrin in human cell lines, including two normal cell lines (WI-38 and foreskin fibroblasts), two transformed cell lines (AV-3 amnionic cells and Chang liver cells), and two neoplastic cell lines (HEp-2, larynx cancer and HeLa, cervical cancer). Transferrin receptors were determined by an indirect immunofluorescence technique based on their ability to bind purified human transferrin. Gallium-67 uptake was determined after a 24-h incubation of cells with Ga-67 in the presence and absence of transferrin (0-2.5 mg/ml). 125I-labeled transferrin uptake was also obtained after a 24-h incubation. The fraction of cells with transferrin receptors was low in normal cell lines (3% and 9%), intermediate with transformed cell lines (33% and 61%). Transferrin stimulated 67Ga uptake by all six cell lines. However, there was poor correlation between the number of transferrin-receptor positive cells and 67Ga uptake either in the presence (r = 0.21) or absence (r = 0.46) of human transferrin. Likewise, there was poor correlation between the number of transferrin-receptor positive cells and 125I-labeled transferrin uptake (r = 0.35). In contrast, the correlation between 67Ga uptake (in the presence of transferrin) and 125I-labeled transferrin uptake was highly significant (r = 0.96). These results suggest that human cell lines in culture are capable of both transferrin-dependent and transferrin-independent uptake of 67Ga.