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 Ga-67 in the form of a Ga-67-transferrin complex via transferrin receptors. As a result, we attempted to determine the influence of hypoxic conditions on Ga-67 uptake in tumour cells. B16 melanoma cells and LS180 colon cancer cells were incubated in 95% air/5% CO2 or 95% N-2/5% CO2 for 1 h at 37 degreesC. Cellular uptake of Ga-67 citrate was subsequently determined at 20, 40, 60 and 90 min. Uptake of the Ga-67-transferrin complex pre-chelated in vitro was similarly assessed. The effect of hypoxia on Ga-67 binding to serum proteins was also investigated. Both B16 and LS180 cells displayed increased cellular uptake of Ga-67 citrate in N-2 gas in comparison to that in air (P < 0.0001). Hypoxia more prominently influenced cellular uptake of Ga-67-transferrin relative to that of Ga-67 citrate (P < 0.0001). Hypoxia did not affect the percentages of Ga-67 radioactivity bound to protein in medium supplemented with fetal calf serum, indicating that the results were not caused by the alteration of Ga-67-transferrin formation. These findings suggest the role of tissue hypoxia with respect to accumulation of Ga-67 in tumours, which is likely mediated by transferrin receptors. ((C) 2004 Lippincott Williams Wilkins).