2-fluoro-2-deoxyglucose-6-phosphate and Neoplasms

Abstract Positron emission tomography (PET) using fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG) has made a major impact in clinical oncology in diagnosing, staging and restaging malignancy as well as in monitoring therapy response. Over the past decade, there has been an enormous growth in the scientific and clinical evidence supporting PET including recent important contribution from the Australian PET Data Collection Project. Since 2001, hybrid PET-computed tomography has also largely replaced PET alone systems with significant improvement in diagnostic accuracy. This review is a brief update on the current status of FDG-PET focusing on its oncologic applications.

Topics: Forecasting; Glucose-6-Phosphate; Humans; Neoplasm Staging; Neoplasms; Positron-Emission Tomography

Progress toward targeting cancer cells is a multi-disciplinary endeavor. In addition to the surgical and oncology specialties, radiologists collaborate with mathematicians, computer scientists, and physicists, in a constant effort to incrementally improve upon the current imaging modalities. Recently, radiologists have formed collaborations with molecular biologists and chemists in order to develop molecular agents that target cancer cells via receptor-substrate or specific physiochemical interactions. In this review, we summarize selected efforts toward molecular targeting of the lymphovascular system. Standard imaging modalities, positron emission tomography, single photon emission tomography, and ultrasound, are reviewed as well as, the targeted introduction of substances for endolymphatic therapy. We also review the current status of sentinel lymph node mapping with radiocolloids and the application of molecular targeting for the development of a radiopharmaceutical specifically designed for sentinel lymph node mapping.

Topics: Animals; Clinical Trials, Phase I as Topic; Diagnostic Imaging; Glucose-6-Phosphate; Humans; Lymph Nodes; Lymphatic Metastasis; Lymphatic System; Lymphography; Lymphoscintigraphy; Neoplasms; Positron-Emission Tomography; Tomography, Emission-Computed, Single-Photon; Ultrasonography

Statins, HMG-CoA reductase inhibitors, are used in the prevention and treatment of cardiovascular diseases owing to their lipid-lowering effects. Previous studies revealed that, by modulating membrane cholesterol content, statins could induce conformational changes in cluster of differentiation 20 (CD20) tetraspanin. The aim of the presented study was to investigate the influence of statins on glucose transporter 1 (GLUT1)-mediated glucose uptake in tumor cells. We observed a significant concentration- and time-dependent decrease in glucose analogs' uptake in several tumor cell lines incubated with statins. This effect was reversible with restitution of cholesterol synthesis pathway with mevalonic acid as well as with supplementation of plasma membrane with exogenous cholesterol. Statins did not change overall GLUT1 expression at neither transcriptional nor protein levels. An exploratory clinical trial revealed that statin treatment decreased glucose uptake in peripheral blood leukocytes and lowered (18)F-fluorodeoxyglucose ((18)F-FDG) uptake by tumor masses in a mantle cell lymphoma patient. A bioinformatics analysis was used to predict the structure of human GLUT1 and to identify putative cholesterol-binding motifs in its juxtamembrane fragment. Altogether, the influence of statins on glucose uptake seems to be of clinical significance. By inhibiting (18)F-FDG uptake, statins can negatively affect the sensitivity of positron emission tomography, a diagnostic procedure frequently used in oncology.

Topics: Blotting, Western; Cell Line, Tumor; Cholesterol; Excitatory Amino Acid Transporter 2; Female; Flow Cytometry; Gene Expression; Glucose; Glucose Transporter Type 1; Glucose-6-Phosphate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Leukocytes; Male; Multimodal Imaging; Neoplasms; Positron-Emission Tomography; Real-Time Polymerase Chain Reaction; Tomography, X-Ray Computed

Progress toward targeting cancer cells is a multi-disciplinary endeavor. In addition to the surgical and oncology specialties, radiologists collaborate with mathematicians, computer scientists, and physicists, in a constant effort to incrementally improve upon the current imaging modalities. Recently, radiologists have formed collaborations with molecular biologists and chemists in order to develop molecular agents that target cancer cells via receptor-substrate or specific physiochemical interactions. In this review, we summarize selected efforts toward molecular targeting of the lymphovascular system. Standard imaging modalities, positron emission tomography, single photon emission tomography, and ultrasound, are reviewed as well as, the targeted introduction of substances for endolymphatic therapy. We also review the current status of sentinel lymph node mapping with radiocolloids and the application of molecular targeting for the development of a radiopharmaceutical specifically designed for sentinel lymph node mapping.

Topics: Animals; Clinical Trials, Phase I as Topic; Diagnostic Imaging; Glucose-6-Phosphate; Humans; Lymph Nodes; Lymphatic Metastasis; Lymphatic System; Lymphography; Lymphoscintigraphy; Neoplasms; Positron-Emission Tomography; Tomography, Emission-Computed, Single-Photon; Ultrasonography

In recent years, the application of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) for voluntary cancer screening of asymptomatic individuals is becoming more and more popular in China. However, the utility of such screening is still controversial.. This study enrolled a total of 1,572 asymptomatic individuals who underwent FDG PET/CT as a part of cancer screening program in Shanghai Ruijin Hospital, between January 2010 and December 2014. Whole set of clinical data of each case was retrospectively collected. The cancer detection rate, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FDG PET/CT were calculated, according to the cancer data obtained from histopathological examinations or at least 12-month clinical follow-up.. Among the 1,572 subjects, malignant tumors were found in 27 cases (1.72%). The cancer detection rate was 2.74% among subjects who were older than 50 years, 4.72% among those who had a family history of malignant tumors, and 2.77% among those whose tumor markers were positive. These rates were higher than those among other subjects (p<0.05). The detection rate of FDG PET/CT in asymptomatic cancer screening was 1.44%, and the sensitivity, specificity, PPV, and NPV were estimated to be 85.19%, 99.68%, 82.14%, and 99.75%, respectively.. Considering its less cost-efficient performance, we do not recommend using FDG PET/CT for cancer screening in asymptomatic population. Nevertheless, FDG PET/CT might be a powerful cancer screening modality with the selection of high-risk group, and an optimal combination of the modalities should be provided in order to maximize diagnostic performance with lower costs.

Topics: Adult; Aged; Aged, 80 and over; Female; Follow-Up Studies; Glucose-6-Phosphate; Humans; Male; Mass Screening; Middle Aged; Neoplasms; Positron-Emission Tomography; Retrospective Studies

To monitor a real-time follow-up of tumor response to photodynamic therapy (PDT) by dynamic 2-deoxy-2-[(18)F]fluoro-d-glucose ((18)FDG) and positron emission tomography (PET) using two photosensitizing drugs in vivo, and to assess their mechanisms of action.. Two types of photosensitizers with different action mechanisms were used in rats implanted with two tumors: AlPcS4 mainly affecting the tumor vascular system, and ZnPcS2 largely inducing direct cell kill. Twenty-four hours after administration of either photosensitizer, one tumor served as control while the other was treated with red light during 30min within the 2h PET imaging by infusion of (18)FDG. The usual two-tissue compartment kinetic model was modified to take into account the perturbation of the treatment during imaging.. The illumination of the tumors during PET imaging provoked a net decrease of (18)FDG uptake in tumors treated with AlPcS4 and a near total absence of (18)FDG uptake in tumors treated with ZnPcS2. After the end of illumination, the tumors regained (18)FDG uptake with a more pronounced uptake in the tumors treated with ZnPcS2. The rate constant values of the new (18)FDG kinetic model reflected the response of the tumors to the treatment in both photosensitizers.. Dynamic PET imaging can be used to quantitatively assess in vivo and in real-time the response of tumors to treatments. It is demonstrated that the 30min of treatment was not sufficient to reduce the activity of the tumors. The technique could be extended to directly monitor the effects of drugs in vivo.

Topics: Animals; Disease Models, Animal; Glucose-6-Phosphate; Indoles; Neoplasms; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Positron-Emission Tomography; Rats

Clustering analysis (CA) and principal component analysis (PCA) were applied to dynamic Cerenkov luminescence images (dCLI). In order to investigate the performances of the proposed approaches, two distinct dynamic data sets obtained by injecting mice with (32)P-ATP and (18)F-FDG were acquired using the IVIS 200 optical imager. The k-means clustering algorithm has been applied to dCLI and was implemented using interactive data language 8.1. We show that cluster analysis allows us to obtain good agreement between the clustered and the corresponding emission regions like the bladder, the liver, and the tumor. We also show a good correspondence between the time activity curves of the different regions obtained by using CA and manual region of interest analysis on dCLIT and PCA images. We conclude that CA provides an automatic unsupervised method for the analysis of preclinical dynamic Cerenkov luminescence image data.

Topics: Adenosine Triphosphate; Algorithms; Animals; Beta Particles; Cluster Analysis; Glucose-6-Phosphate; Image Processing, Computer-Assisted; Liver; Luminescent Measurements; Mice; Mice, Nude; Molecular Imaging; Neoplasms; Phosphorus Radioisotopes; Principal Component Analysis; Radioactive Tracers; Radionuclide Imaging; Radiopharmaceuticals; Transplantation, Heterologous; Urinary Bladder

The phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascade is an important component of the insulin signaling in normal tissues leading to glucose uptake and homeostasis and for cell survival signaling in cancer cells. Hyperglycemia is an on-target side effect of many inhibitors of PI3K/Akt signaling including the specific PI3K inhibitor PX-866. The peroxisome proliferator-activated receptor gamma agonist pioglitazone, used to treat type 2 diabetes, prevents a decrease in glucose tolerance caused by acute administration of PX-866. Our studies have shown that pioglitazone does not inhibit the antitumor activity of PX-866 in A-549 non-small cell lung cancer and HT-29 colon cancer xenografts. In vitro studies also showed that pioglitazone increases 2-[1-(14)C]deoxy-D-glucose uptake in L-6 muscle cells and prevents inhibition of 2-deoxyglucose uptake by PX-866. Neither pioglitazone nor PX-866 had an effect on 2-deoxyglucose uptake in A-549 lung cancer cells. In vivo imaging studies using [18F]2-deoxyglucose (FDG) positron emission tomography showed that pioglitazone increases FDG accumulation by normal tissue but does not significantly alter FDG uptake by A-549 xenografts. Thus, peroxisome proliferator-activated receptor gamma agonists may be useful in overcoming the increase in blood glucose caused by inhibitors of PI3K signaling by preventing the inhibition of normal tissue insulin-mediated glucose uptake without affecting antitumor activity.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Disease Progression; Glucose; Glucose Transport Proteins, Facilitative; Glucose-6-Phosphate; Gonanes; Humans; Hyperglycemia; Mice; Neoplasms; Phosphatidylinositol 3-Kinases; Pioglitazone; PPAR gamma; Signal Transduction; Thiazolidinediones; Xenograft Model Antitumor Assays

Fluorine-18-2-fluoro-2-deoxy-D-glucose (18F-FDG) injectable was developed as a tumor imaging agent reflecting glucose metabolism. In membrane transportation studies, the uptake of 14C-FDG into erythrocytes decreased with an increase in glucose concentration, and Cytochalasin B, inhibitor of glucose transporter (GLUT), blocked the uptake about 75%. The results means FDG is transported into tumor cells mainly by GLUT as glucose analogues. 18F-FDG is recognized to be phosphorylated to 18F-FDG-6-phosphate with hexokinase. We found that FDG-6-phosphate was further isomerized to 18F-FDM-6-phosphate by phosphoglucose isomerase (PGI) in vitro. About 27% 18F-FDM-6-phosphate was generated at the reaction with 70 U PGI for 90 min. These results show that the 18F-FDG injectable manufactured by the commercial supply system has equivalent properties; membrane transportation characteristic and enzyme affinity, to FDG synthesized at each PET institution.

Topics: Animals; Erythrocytes; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Glucose-6-Phosphate; Hexokinase; Monosaccharide Transport Proteins; Neoplasms; Phosphorylation; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Tomography, Emission-Computed