Ong L-C, Jin Y, Song I-C, Yu S, Zhang K, Chow P K H
Singapore General Hospital, Singapore National Cancer Centre, Singapore.
Acta Radiol. 2008 Dec;49(10):1145-53. doi: 10.1080/02841850802482486.
The uptake of 2-[18F]-2-deoxy-D-glucose ((18)F-FDG) is widely used as a marker of increased glucose metabolism to monitor progression of cancers with positron emission tomography (PET). Many tumors have been shown to overexpress facilitated glucose transporters, especially GLUT-1 and a glycolytic enzyme, hexokinase II.
To define whether a quantitative relationship exists between the expression levels of GLUT-1 and hexokinase II, and (18)F-FDG uptake in human cancer xenografts.
We determined the expression levels of both GLUT-1 and hexokinase II in normal cells and in five different human cancer cell lines (AGS, A431, A549, Colo 320 HSR, and HepG2) using Western blot analysis. In vitro assays of 18F-FDG uptake in cultures were performed, and subsequently representative cell lines were inoculated onto the flanks of severe combined immunodeficient (SCID) mice. To establish an orthotopic model of human hepatocellular carcinoma (HCC), cells were injected into the intraportal vein of SCID mice. (18)F-FDG uptake in vivo was assessed by subjecting mice to PET imaging.
All cell lines were shown to express higher amounts of GLUT-1 and hexokinase II compared with fibroblast controls. Our results from in vitro (18)F-FDG uptake assays also correlated with the Western blot results. All xenografts gave highly positive results at microPET imaging, and a strong correlation (R(2)=0.88, P<0.001) was found between the maximum standardized uptake values (SUV(max)) and the expression of GLUT-1 proteins.
Our data indicate that the expression levels of GLUT-1 and hexokinase II as well as in vitro assays of FDG uptake serve as good screening tests to evaluate the feasibility of cell lines to be further developed into xenograft cancer models for small-animal PET imaging.
2-[18F]-2-脱氧-D-葡萄糖（(18)F-FDG）摄取作为葡萄糖代谢增加的标志物，被广泛用于通过正电子发射断层扫描（PET）监测癌症进展。许多肿瘤已被证明过度表达易化葡萄糖转运蛋白，尤其是葡萄糖转运蛋白1（GLUT-1）和一种糖酵解酶，己糖激酶II。
确定GLUT-1和己糖激酶II的表达水平与人类癌症异种移植瘤中(18)F-FDG摄取之间是否存在定量关系。
我们使用蛋白质印迹分析确定了正常细胞以及五种不同人类癌细胞系（AGS、A431、A549、Colo 320 HSR和HepG2）中GLUT-1和己糖激酶II的表达水平。进行了培养物中18F-FDG摄取的体外测定，随后将代表性细胞系接种到严重联合免疫缺陷（SCID）小鼠的胁腹。为建立人类肝细胞癌（HCC）原位模型，将细胞注入SCID小鼠的门静脉。通过对小鼠进行PET成像评估体内(18)F-FDG摄取。
与成纤维细胞对照相比，所有细胞系均显示出更高水平的GLUT-1和己糖激酶II表达。我们体外18F-FDG摄取测定的结果也与蛋白质印迹结果相关。所有异种移植瘤在微型PET成像中均给出高度阳性结果，并且在最大标准化摄取值（SUV(max)）与GLUT-1蛋白表达之间发现了强相关性（R(2)=0.88，P<0.001）。
我们的数据表明，GLUT-1和己糖激酶II的表达水平以及FDG摄取的体外测定可作为良好的筛选试验，以评估细胞系进一步开发成用于小动物PET成像的异种移植癌模型的可行性。
