2-[18F]-2-deoxy-D-glucose (FDG) uptake in human tumor cells is related to the expression of GLUT-1 and hexokinase II.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Ong
L-C
LC
Singapore General Hospital, Singapore National Cancer Centre, Singapore.
Jin
Y
Y
Song
I-C
IC
Yu
S
S
Zhang
K
K
Chow
P K H
PK
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005240:Feasibility Studies; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis*; D006593:Hexokinase / Q000096:biosynthesis*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D051272:Glucose Transporter Type 1; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D006593:Hexokinase