title: Molecular mechanisms of [18F]fluorodeoxyglucose accumulation in liver cancer.
abstract: To elucidate the molecular mechanisms underlying the insufficient sensitivity in the detection of hepatocellular carcinoma (HCC) by [18F] 2-ﬂuoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), the characteristics of glucose metabolism-related protein expression in HCC were examined in liver metastasis from colorectal cancer (Meta). Thirty-four patients (14 Meta and 20 HCC) who underwent FDG-PET and hepatectomy were studied. The relationships between the maximum standardized uptake value (SUV) in tumors and the mRNA expression of glucose metabolism-related proteins [hexokinase (HK), glucose transporter 1 (GLUT1), and glucose-6-phosphatase (G6Pase)] and proliferating cell nuclear antigen (PCNA) were examined in snap-frozen specimens with quantitative PCR. Tumor detection rates were lower in HCC (15/20) compared to Meta (13/14) patients. HK and GLUT1 expression was lower and G6Pase expression was higher in HCC compared to Meta. In particular, GLUT1 overexpression was 92-fold in Meta and 11-fold in HCC compared to the surrounding liver. The SUV correlated with GLUT1 and PCNA expression in HCC, but not Meta patients. Of note, four cases of poorly differentiated (P/D) HCC compared to moderately differentiated (M/D) HCC produced completely different results for FDG uptake (SUV, 14.4 vs. 4.0) and mRNA expression (G6Pase expression, 0.007 vs. 1.5). Variations in the expression of glucose metabolism-related enzymes between HCC and Meta patients are attributed to origin or degree of differentiation. Low FDG uptake in M/D HCC reflected low GLUT1 and high G6Pase expression, while high FDG accumulation in P/D HCC could reflect increased GLUT1 and decreased G6Pase expression. These results may explain why M/D HCC is not detected as sensitively by FDG-PET.
authors.affiliation: Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Miki, Kita, Kagawa 761-0793, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Izuishi
authors.affiliation: Department of Radiology, Faculty of Medicine, Kagawa University, Miki, Kita, Kagawa 761-0793, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Internal Medicine of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Miki, Kita, Kagawa 761-0793, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Mori
authors.affiliation: Department of Radiology, Faculty of Medicine, Kagawa University, Miki, Kita, Kagawa 761-0793, Japan.
authors.forename: Riko
authors.initials: R
authors.lastname: Kameyama
authors.affiliation: Department of Internal Medicine of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Miki, Kita, Kagawa 761-0793, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Fujihara
authors.affiliation: Department of Internal Medicine of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Miki, Kita, Kagawa 761-0793, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Masaki
authors.affiliation: Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Miki, Kita, Kagawa 761-0793, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000601:surgery; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000032:analysis / Q000235:genetics; D051273:Glucose Transporter Type 2 / Q000032:analysis; D005952:Glucose-6-Phosphatase / Q000235:genetics / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives / Q000737:chemistry; D006498:Hepatectomy; D006593:Hexokinase / Q000032:analysis / Q000235:genetics; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000601:surgery; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D019275:Radiopharmaceuticals
chemical_list: D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D019275:Radiopharmaceuticals; C495677:SLC2A1 protein, human; C495680:SLC2A2 protein, human; D019788:Fluorodeoxyglucose F18; C047515:2-fluoro-2-deoxyglucose-6-phosphate; D019298:Glucose-6-Phosphate; D006593:Hexokinase; D005952:Glucose-6-Phosphatase; D005947:Glucose