Common Pathway for Tumor Cell Uptake of gallium-67 and iron-59 via a Transferrin Receptor

J Natl Cancer Inst. 1980 Jan;64(1):41-53.

Abstract

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.

MeSH terms

  • Animals
  • Biological Transport, Active
  • Female
  • Gallium / metabolism*
  • Gallium Radioisotopes
  • Iron / metabolism*
  • Iron Radioisotopes
  • Kinetics
  • Mammary Neoplasms, Experimental / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Models, Biological
  • Molecular Weight
  • Receptors, Cell Surface* / isolation & purification
  • Transferrin / metabolism*

Substances

  • Gallium Radioisotopes
  • Iron Radioisotopes
  • Receptors, Cell Surface
  • Transferrin
  • Gallium
  • Iron