Clinicopathological presentation of varying 18 F-FDG uptake and expression of glucose transporter 1 and hexokinase II in cases of hepatocellular carcinoma and cholangiocellular carcinoma (original) (raw)

In vivo assessment of glucose metabolism in hepatocellular carcinoma with FDG-PET

Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1995

The present study was designed to assess glucose metabolism in hepatocellular carcinoma (HCC) with PET and [18F]fluorodeoxyglucose (FDG) and to compare the results with the measured in vitro enzymatic activity of glucose metabolism and the histologic grading of HCC. Dynamic FDG-PET scans were obtained in 17 preoperative patients with HCC. From the serial tissue and arterial radioactivities obtained by dynamic PET, FDG kinetic rate constants (K1 to k4) were obtained. The standardized uptake value (SUV) was also determined from the images acquired 48 to 60 min after FDG administration. These PET results were compared with hexokinase and glucose-6-phosphatase (G6Pase) activities and histologic grading of HCC in surgically resected tumor materials. According to histologic grading, the tumors were divided into low-grade and high-grade HCCs. The k3 and SUV of high-grade HCCs were significantly higher than those of low-grade HCCs (p < 0.005, each). In addition, high correlations were ob...

Relationship between retention index in dual-phase (18)F-FDG PET, and hexokinase-II and glucose transporter-1 expression in pancreatic cancer

Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2002

Recently, some studies have shown that delayed scanning with (18)F-FDG PET may help to differentiate malignant from benign pancreatic lesions. However, no study has evaluated the relationship between temporal changes in (18)F-FDG uptake and expression of hexokinase or glucose transporter. Twenty-one consecutive patients with pancreatic cancer were studied preoperatively by dual-phase (18)F-FDG PET, performed 1 and 2 h after injection of (18)F-FDG. The standardized uptake value (SUV) of the pancreatic cancer was determined, and the retention index (RI) (%) was calculated by subtracting the SUV at 1 h (SUV1) from the SUV at 2 h (SUV2) and dividing by SUV1. The percentages of cells strongly expressing hexokinase type-II (HK-II) and glucose transporter-1 (GLUT-1) were scored on a 5-point scale (1 = 0%-20%, 2 = 20%-40%, 3 = 40%-60%, 4 = 60%-80%, 5 = 80%-100%) by visual analysis of immunohistochemical staining of paraffin sections from the tumor specimens using anti-HK-II and anti-GLUT-1 ...

Reduction in the expression of glucose transporter protein GLUT 2 in preneoplastic and neoplastic hepatic lesions and reexpression of GLUT 1 in late stages of hepatocarcinogenesis

Cancer research, 1993

Expression of two important glucose transporter proteins, GLUT 2 (which is the typical glucose transporter in hepatocytes of adult liver) and the erythroid/brain type glucose transporter GLUT 1 (representing the typical glucose transporter in fetal liver parenchyma), was studied immunocytochemically during hepatocarcinogenesis in rats at different time points between 7 and 65 wk after cessation of 7-wk administration of 12 mg/kg of body weight of N-nitrosomorpholine p.o. (stop model). Foci of altered hepatocytes excessively storing glycogen (GSF) and mixed cell foci (MCF) composed of both glycogenotic and glycogen-poor cells were present at all time points studied. Seven wk after withdrawal of the carcinogen, GSF were the predominant type of focus of altered hepatocytes. Morphometrical evaluation of the focal lesions revealed that the number and volume fraction of GSF increased steadily until Wk 65. MCF were rare at 7 wk, increased slightly in number and size until Wk 37, but showed...

{"__content__"=>"Preoperative metabolic tumor volume of intrahepatic cholangiocarcinoma measured by F-FDG-PET is associated with the KRAS mutation status and prognosis.", "sup"=>{"__content__"=>"18"}}

Journal of translational medicine, 2018

Surgical resection remains the mainstay of curative treatment for intrahepatic cholangiocarcinoma (ICC). Prognosis after surgery is unsatisfactory despite improvements in treatment and post-operative clinical management. Despite developments in the molecular profiling of ICC, the preoperative prediction of prognosis remains a challenge. This study aimed to identify clinical prognostic indicators by investigating the molecular profiles of ICC and evaluating the preoperative imaging data of F-fluorodeoxyglucose positron emission tomography (F-FDG-PET). A retrospective analysis was performed on 50 consecutive patients with ICC who underwent curative hepatectomy after F-FDG-PET examination. To evaluate the molecular profiles of ICC, KRAS mutation status was assessed in resected specimens. For the assessment of glucose uptake, we observed the expression of glucose transporter-1 (GLUT-1) by immunohistochemistry. The data of F-FDG-PET were re-evaluated as follows: maximum standardized upta...

Evaluation of Metabolic Characteristics and Viability of Lipiodolized Hepatocellular Carcinomas Using 18F-FDG PET/CT

Journal of Nuclear Medicine, 2010

This study aimed to evaluate the metabolic characteristics of lipiodolized hepatocellular carcinomas (HCCs) and the diagnostic accuracy of 18 F-FDG PET/CT in assessing the viability of lipiodolized HCCs. Methods: Thirty-six patients (age range, 32-73 y) with 38 lipiodolized HCCs who had undergone transcatheter arterial chemoembolization (TACE) with lipiodol before 18 F-FDG PET/CT (2-434 d) and 55 patients (age range, 36-77 y) with 57 treatment-naïve HCCs who had not been treated with TACE were retrospectively studied. All patients underwent hepatic lobectomy or transplantation within 1 mo after PET/CT and multiphasic contrast-enhanced CT. 18 F-FDG uptake by lipiodolized and naïve HCCs was compared and correlated with tumor size, pathologic grade, serum a-fetoprotein (AFP) concentration, and time interval between TACE and PET/CT. The diagnostic accuracy of PET/CT and contrast-enhanced CT in evaluating the viability of lipiodolized HCC was compared. Results: Histologic examination showed 30 viable and 8 nonviable lipiodolized HCCs. Of the 30 viable tumors, 19 showed increased, 10 similar, and 1 decreased 18 F-FDG uptake. Of the 8 nonviable HCCs, 3 showed increased and 5 decreased 18 F-FDG uptake. Uptake by viable lipiodolized HCCs was correlated with tumor size (P , 0.05) but not correlated with pathologic grade, AFP concentration, or interval between TACE and PET/ CT. In contrast, 18 F-FDG uptake by naïve HCCs was significantly correlated with tumor size and pathologic grade (P , 0.05 for each comparison). When lipiodolized HCCs with 18 F-FDG uptake that was greater than or similar to that in the surrounding normal liver were considered viable, the diagnostic sensitivity of PET/CT and contrast-enhanced CT in the early postembolic period (,3 mo) was 100% and 94%, respectively, and that in the late postembolic period was 93% and 79%, respectively. The specificity of 18 F-FDG PET/CT and contrastenhanced CT was 63% and 100%, respectively, in the acute period. Three viable lipiodolized HCCs with high AFP concentration were true-positives on PET/CT but false-negatives on contrast-enhanced CT images. Conclusion: After TACE, 18 F-FDG uptake in lipiodolized HCCs was not correlated with pathologic grade, in contrast to uptake in treatment-naïve HCCs. 18 F-FDG PET/CT showed a high diagnostic sensitivity in assessing the viability of lipiodolized HCCs, with moderate specificity. This method may be useful in determining the viability of lipiodolized HCCs in patients with increased serum AFP concentration or normal results on contrast-enhanced CT images.

Dynamic PET with (18)F-Deoxyglucose (FDG) and quantitative assessment with a two-tissue compartment model reflect the activity of glucose transporters and hexokinases in patients with colorectal tumors

American journal of nuclear medicine and molecular imaging, 2013

Dynamic PET (dPET) with (18)F-Deoxyglucose (FDG) provides quantitative information about distribution of the tracer in a predefined volume over time. A two-tissue compartment model can be used to obtain quantitative data regarding transport of FDG into and out of the cells, phosphorylation and dephosphorylation rate of intracellular FDG, and fractional blood volume in the target volume, also named vessel density. Aim of the study was the correlation of glucose transporters expression and hexokinases with the corresponding compartment parameters.Patients with colorectal tumors were examined with dynamic PET prior to surgery. Afterwards, tumor samples were obtained during surgery and gene expression was assessed using gene arrays. The dynamic PET data were evaluated to quantify the parameters of a two tissue compartment model for colorectal tumors using a Volume-of-Interest (VOI) technique. A multiple correlation/regression analysis was performed using glucose transporters as independ...

P-glycoprotein expression affects 18F-fluorodeoxyglucose accumulation in hepatocellular carcinoma in vivo and in vitro

18 F-fluorodeoxyglucose (FDG) uptake in hepatocellular carcinoma (HCC) is associated with tumor differentiation and expression of P-glycoprotein (P-gp), a drug efflux pump that plays an important role in chemoresistance. The aim of the study was to clarify the factors that affects FDG uptake in HCC in vivo and in vitro. The standardized uptake value (SUV) and the tumor to non-tumor SUV ratio (TNR) for FDG uptake in HCC in vivo was determined by FDG-PET in 28 patients. Expression levels of glucose transporter-1 (GLUT-1), GLUT-2 and type II hexokinase (HK-II) were examined immunohistochemically in resected specimens. The glucose-6-phosphatase (G-6-Pase) activity was determined in tissue homogenates. In vitro, PLC/PRF/5 cells and doxorubicin-resistant PLC/DOR cells were used to examine the effect of P-gp on FDG uptake. The effects of two P-gp inhibitors, verapamil and cepharanthine, on accumulation of FDG were also examined. In vivo, GLUT-1 expression was low in HCCs, but was significantly higher in poorly differentiated HCCs than in moderately differentiated HCCs (P=0.043) and was positively correlated with SUV (r=0.75, P<0.0001) and TNR (r=0.7, P<0.

Fluorine-18 Fdg Positron Emission Tomography for Imaging of Hepatocellular Carcinoma

American Journal of Gastroenterology, 1999

OBJECTIVE: The detection of increased fluorine-18 fluorodeoxyglucose (18 F-FDG) uptake by positron emission tomography (PET) is based on the enhanced glucose metabolism of tumor cells. Because the detection and staging of hepatocellular carcinoma (HCC) in patients with liver cirrhosis can be difficult, we prospectively evaluated the sensitivity of 18 F-FDG PET in 14 consecutive patients with HCC. METHODS: Whole body and regional 18 F-FDG PET of the liver were obtained. The results were compared with ultrasonography, contrast-enhanced, helical CT, histological grading, p53 protein expression of HCC, and serum ␣-fetoprotein (AFP) level. RESULTS: In 7 patients PET demonstrated increased tumor 18 F-FDG uptake, whereas HCC was not distinguishable from nonmalignant liver tissue in 7 other patients. Hepatic lesions were detected by ultrasonography in all patients, whereas only 11 of 14 HCCs could be identified by CT. In 3 patients extrahepatic spread was demonstrated by 18 F-FDG PET. Patients with increased tumor 18 F-FDG uptake had significantly larger hepatic lesions and higher serum AFP levels than those with normal 18 F-FDG uptake. Lesions could be visualized by 18 F-FDG PET in 7 of 8 patients with moderately or poorly differentiated HCC, whereas none of the six well-differentiated tumors was detected. Two patients with strong p53 expression demonstrated increased tumor 18 F-FDG uptake and extrahepatic metastases. CONCLUSIONS: The sensitivity of 18 F-FDG PET for the imaging of HCC is low. Nevertheless, in patients with moderately or poorly differentiated HCC, tumors Ͼ5 cm, or with markedly elevated AFP levels 18 F-FDG PET may contribute to an effective noninvasive staging.