Common pathway for tumor cell uptake of gallium-67 and iron-59 via a transferrin receptor.
We studied the tumor uptake of [67Ga]citrate, [59Fe]citrate, and 125I-labeled transferrin (TF) by the in vitro growth form of EMT-6, a sarcoma-like mammary tumor of BALB/c mice. In analyzing the binding experiments, we developed a new mathematical model based on a formulation originally used to express the interaction of hormones with specific tissue receptors. The uptake of both carrier-free 67Ga and 59Fe by tumor cells was mediated by kinetically identical TF receptors. We also studied teric acid extracts of the stroma of EMT-6 tumors grown both in vivo and in vitro. Chromatography of these extracts on Sephacryl S-200 SF demonstrated that the cellular stroma contained specific TF-binding macromolecules. On the basis of these findings, we proposed the "transferrin receptor hypothesis" for the mechanism of 67Ga uptake by tumors. According to this view, a tumor-associated TF receptor is the functional unit responsible for the affinity of gallium for certain neoplasms. This receptor was also active in the uptake of iron by tumors.
D000818:Animals; D001693:Biological Transport, Active; D005260:Female; D005708:Gallium / Q000378:metabolism*; D005710:Gallium Radioisotopes; D007501:Iron / Q000378:metabolism*; D007504:Iron Radioisotopes; D007700:Kinetics; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D008970:Molecular Weight; D011956:Receptors, Cell Surface / Q000302:isolation & purification; D014168:Transferrin / Q000378:metabolism*
D005710:Gallium Radioisotopes; D007504:Iron Radioisotopes; D011956:Receptors, Cell Surface; D014168:Transferrin; D005708:Gallium; D007501:Iron