Fluorodeoxyglucose uptake in human cancer cell lines is increased by hypoxia.
Fluorodeoxyglucose uptake in human cancer cell lines is increased by hypoxia.
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发表时间：
1995-09
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通讯作者：
A. Clavo;Raya S. Brown;R. Wahl
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作者：
A. Clavo;Raya S. Brown;R. Wahl
未标记的恶性肿瘤通常具有葡萄糖利用率增加、血流灌注不良和低氧区域。切除肿瘤的放射自显影研究显示，肿瘤坏死区附近的活细胞摄取FDG增加。我们在体外评估肿瘤细胞对FDG的摄取是否随着缺氧而增加。方法将人卵巢癌细胞株HTB 6 3和HTB 77 IP3分别置于0%~2 0%O2气氛中不同时间后，测定细胞对3 H FDG的摄取。葡萄糖转运以及GLUT-1葡萄糖转运体膜蛋白水平的估计被独立地确定。结果轻度低氧(5%O2)1.5h后，黑色素瘤细胞和卵巢癌细胞对FDG的摄取均显著增加(分别为39.6%±6.7%和36.7%+/-9%)。1.5%O2暴露4小时后，FDG摄取增加较大，分别为52.3%+/-8.9%和43.5%+/-19%。缺氧4小时后，黑色素瘤和卵巢癌细胞摄取FDG的能力较基础状态分别增加42.7%+/-10%和63.3%+/-13.7%。3-O-甲基葡萄糖(3-OMG)膜转运在低氧条件下对黑色素瘤和卵巢癌有促进作用。GLUT-1的免疫化学检测显示，暴露在低氧环境下的细胞GLUT-1转运体的膜表达增加。结论低氧可增加两种不同的人恶性肿瘤细胞对FDG的摄取。葡萄糖转运的增加，部分是由于GLUT-1葡萄糖转运体的膜表达增加，导致了这种现象。在PET成像中，肿瘤内FDG摄取的增加可能部分反映了肿瘤的缺氧。
UNLABELLED Malignant neoplasms commonly have increased rates of glucose utilization, poor perfusion and areas of low oxygenation. Autoradiographic studies of excised tumors have shown increased FDG uptake in viable cells near necrotic portions of tumor. We evaluated in vitro whether tumor cell FDG uptake increased with hypoxia. METHODS The uptake of 3H-FDG into two human tumor cell lines (HTB 63 melanoma and HTB 77 IP3 ovarian carcinoma) was determined after exposure to differing oxygen atmospheres ranging from 0% to 20% O2 for varying time periods. Glucose transport was independently determined as well as estimates of the level of Glut-1 glucose transporter membrane protein. RESULTS FDG uptake in both the melanoma and the ovarian carcinoma cell lines increased significantly (39.6% +/- 6.7% and 36.7% +/- 9%, respectively) over basal (20% O2) conditions when cells were exposed to a mild hypoxic environment (5% O2) for 1.5 hr. With a 4-hr exposure to 1.5% O2, the increase in FDG uptake was greater at 52.3% +/- 8.9% and 43.5% +/- 19%, respectively. With 4 hr of anoxia, the increase in FDG uptake over basal conditions was 42.7% +/- 10% and 63.3% +/- 13.7% for melanoma and ovarian carcinoma cells, respectively. Membrane transport of 3-O-methylglucose (3-OMG) was increased by hypoxia for melanoma and ovarian carcinoma. Immunochemical assays for Glut-1 showed an increase in the membrane expression of the Glut-1 transporter in cells exposed to hypoxia. CONCLUSION Hypoxia increases cellular uptake of FDG in two different malignant human cell lines. Increased glucose transport, in part due to increased membrane expression of the Glut-1 glucose transporter, contributes to this phenomenon. Increased FDG uptake in tumors visualized during PET imaging may be partly reflective of tumor hypoxia.