title: Hypoxia as a factor for 67Ga accumulation in tumour cells.
abstract: Recent reports have demonstrated that hypoxia induces the up-regulation of transferrin receptor expression in tumour cells. Tumour cells take up 67Ga in the form of a 67Ga-transferrin complex via transferrin receptors. As a result, we attempted to determine the influence of hypoxic conditions on 67Ga uptake in tumour cells. B16 melanoma cells and LS180 colon cancer cells were incubated in 95% air/5% CO2 or 95% N2/5% CO2 for 1 h at 37 degrees C. Cellular uptake of 67Ga citrate was subsequently determined at 20, 40, 60 and 90 min. Uptake of the 67Ga-transferrin complex pre-chelated in vitro was similarly assessed. The effect of hypoxia on 67Ga binding to serum proteins was also investigated. Both B16 and LS180 cells displayed increased cellular uptake of 67Ga citrate in N2 gas in comparison to that in air (P < 0.0001). Hypoxia more prominently influenced cellular uptake of Ga-transferrin relative to that of 67Ga citrate (P < 0.0001). Hypoxia did not affect the percentages of 67Ga radioactivity bound to protein in medium supplemented with fetal calf serum, indicating that the results were not caused by the alteration of 67Ga-transferrin formation. These findings suggest the role of tissue hypoxia with respect to accumulation of 67Ga in tumours, which is likely mediated by transferrin receptors.
authors.affiliation: Department of Biotracer Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan. kinuya@med.kanazawa-u.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Kinuya
authors.forename: X F
authors.initials: XF
authors.lastname: Li
authors.forename: K
authors.initials: K
authors.lastname: Yokoyama
authors.forename: H
authors.initials: H
authors.lastname: Mori
authors.forename: K
authors.initials: K
authors.lastname: Shiba
authors.forename: N
authors.initials: N
authors.lastname: Watanabe
authors.forename: N
authors.initials: N
authors.lastname: Shuke
authors.forename: H
authors.initials: H
authors.lastname: Bunko
authors.forename: T
authors.initials: T
authors.lastname: Michigishi
authors.forename: N
authors.initials: N
authors.lastname: Tonami
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000378:metabolism; D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002951:Citrates / Q000493:pharmacokinetics*; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005708:Gallium / Q000493:pharmacokinetics*; D006801:Humans; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D051379:Mice; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014168:Transferrin / Q000378:metabolism*
chemical_list: D002951:Citrates; D019275:Radiopharmaceuticals; D014168:Transferrin; D005708:Gallium; C103850:gallium citrate