Hypoxia as a factor for 67Ga accumulation in tumour cells

Recent reports have demonstrated that hypoxia induces the up-regulation of transferrin receptor expression in tumour cells. Tumour cells take up 6 7 Ga in the form of a 6 7 Ga-transferrin complex via transferrin receptors. As a result, we attempted to determine the influence of hypoxic conditions on 6 7 Ga uptake in tumour cells. B16 melanoma cells and LS180 colon cancer cells were incubated in 95% air/5% CO 2 or 95% N 2 /5% CO 2 for 1 h at 37°C. Cellular uptake of 6 7 Ga citrate was subsequently determined at 20, 40, 60 and 90 min. Uptake of the 6 7 Ga-transferrin complex pre-chelated in vitro was similarly assessed. The effect of hypoxia on 6 7 Ga binding to serum proteins was also investigated. Both B16 and LS180 cells displayed increased cellular uptake of 6 7 Ga citrate in N 2 gas in comparison to that in air (P<0.0001). Hypoxia more prominently influenced cellular uptake of 6 7 Ga-transferrin relative to that of 6 7 Ga citrate (P<0.0001). Hypoxia did not affect the percentages of 6 7 Ga radioactivity bound to protein in medium supplemented with fetal calf serum, indicating that the results were not caused by the alteration of 6 7 Ga-transferrin formation. These findings suggest the role of tissue hypoxia with respect to accumulation of 6 7 Ga in tumours, which is likely mediated by transferrin receptors.