Transferrin receptors and gallium-67 uptake in vitro

Abstract

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.

Intrinsic and Acquired Forms of Resistance against the Anticancer Ruthenium Compound KP1019 [Indazoliumtrans-[tetrachlorobis(1H-indazole)ruthenate (III)] (FFC14A)

“…These results correspond with published experiments that demonstrated that binding to iron-loaded transferrin enhances the cellular accumulation of KP1019 . Cancer cells generally express elevated levels of TfR to serve their higher need for iron (Chen et al, 1982). This leads to preferential accumulation of KP1019 in tumor tissue and might explain the limited toxicity of KP1019 in animals (Keppler et al, 1989) and cancer patients (M. E. Scheulen, personal communication).…”

Evaluating the possible role of 68Ga-citrate PET/CT in the characterization of indeterminate lung lesions

“…Gallium acts as an iron analog, the majority of which is bound to transferrin in plasma and then internalized as a gallium-transferrin complex into cells with expression of transferrin receptors. Other localization mechanisms include binding to lactoferrin, siderophores and leukocytes [8,10,11].…”

Iron–Sulfur Cluster Biogenesis as a Critical Target in Cancer

“…Despite not being an Fe-S cluster, the di-Fe center in ribonucleotide reductase is also formed using the CIA Physiologically, Ga 3+ can bind to transferrin in circulation like Fe 3+ and be taken into cells via transferrin-receptor mediated endocytosis [156]. Once inside the cell, Ga 3+ can act as an antagonist to divalent metal ions (e.g., Fe 2+ ) [157] and also be transferred into ferritin supporting its antagonism with Fe [158,159]. The cytotoxicity of Ga 3+ is likely related to its ability to inhibit Fe-containing proteins such as ribonucleotide reductase [155,160].…”