Identifying G6PC3 as a Potential Key Molecule in Hypoxic Glucose Metabolism of Glioblastoma Derived from the Depiction of 18F-Fluoromisonidazole and 18F-Fluorodeoxyglucose Positron Emission Tomography
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SUBMITTER: Okamoto M
PROVIDER: S-EPMC10917478 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:The standardized uptake value (SUV), an indicator of the glucose uptake degree in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), has been used as a prognostic factor in malignant tumors. We aimed to identify a signature reflecting prognostic SUV characteristics in breast cancer (BRC). Transcriptome profiling was performed to identify a signature associated with the SUV in BRC patients who underwent preoperative FDG-PET. We defined a signature consisting of 723 genes significantly correlated with the SUV (|r| > .35; P < .001). The patient subgroups classified by the signature were significantly similar to those classified by the SUV (odds ratio, 8.02; 95% CI, 2.45 to 29.3; P < 0.001). The SUV signature showed independent clinical utility for predicting BRC prognosis (hazard ratio, 1.25; 95% CI, 1.11 to 1.42; P < 0.001). Integrative analysis demonstrated a significance of the signature in predicting the response to immunotherapy and revealed that a signaling axis defined by TP53-FOXM1 and its downstream effectors in glycolysis-gluconeogenesis, including LDHA, might be important mediators in the FDG-PET process. Our results reveal characteristics of glucose uptake captured by FDG-PET, supporting an understanding of glucose metabolism as well as poor prognosis in BRC patients with a high SUV.
2020-03-18 | GSE131769 | GEO
Project description:The standardized uptake value (SUV), an indicator of the glucose uptake degree in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), has been used as a prognostic factor in malignant tumors. We aimed to identify a signature reflecting prognostic SUV characteristics in triple negative breast cancer (TNBC). Transcriptome profiling was performed to identify a signature associated with the SUV in TNBC patients who underwent preoperative FDG-PET. We defined a signature significantly associated with the SUV (|r| > .35; P < .01). The SUV signature showed independent clinical utility for predicting BRC prognosis. Integrative analysis demonstrated a significance of the signature in predicting the response to immunotherapy and revealed that a signaling axis defined by TP53-FOXM1 and its downstream effectors in glycolysis-gluconeogenesis, including LDHA, might be important mediators in the FDG-PET process. Our results reveal characteristics of glucose uptake captured by FDG-PET, supporting an understanding of glucose metabolism as well as poor prognosis in TNBC patients with a high SUV.
2020-03-18 | GSE135565 | GEO
Project description:In this study, we show a basis function method (BAFPIC) for voxelwise calculation of kinetic parameters (K(1), k(2), k(3), K(i)) and blood volume using an irreversible two-tissue compartment model. BAFPIC was applied to rat ischaemic stroke micro-positron emission tomography data acquired with the hypoxia tracer [(18)F]fluoromisonidazole because irreversible two-tissue compartmental modelling provided good fits to data from both hypoxic and normoxic tissues. Simulated data show that BAFPIC produces kinetic parameters with significantly lower variability and bias than nonlinear least squares (NLLS) modelling in hypoxic tissue. The advantage of BAFPIC over NLLS is less pronounced in normoxic tissue. K(i) determined from BAFPIC has lower variability than that from the Patlak-Gjedde graphical analysis (PGA) by up to 40% and lower bias, except for normoxic tissue at mid-high noise levels. Consistent with the simulation results, BAFPIC parametric maps of real data suffer less noise-induced variability than do NLLS and PGA. Delineation of hypoxia on BAFPIC k(3) maps is aided by low variability in normoxic tissue, which matches that in K(i) maps. BAFPIC produces K(i) values that correlate well with those from PGA (r(2)=0.93 to 0.97; slope 0.99 to 1.05, absolute intercept <0.00002 mL/g per min). BAFPIC is a computationally efficient method of determining parametric maps with low bias and variance.
| S-EPMC3049519 | biostudies-literature
Project description:RationaleFew noninvasive biomarkers for pulmonary inflammation are currently available that can assess the lung-specific response to antiinflammatory treatments. Positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) is a promising new method that can be used to quantify pulmonary neutrophilic inflammation.ObjectivesTo evaluate the ability of FDG-PET to measure the pulmonary antiinflammatory effects of hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and recombinant human activated protein C (rhAPC) in a human model of experimentally-induced lung inflammation.MethodsEighteen healthy volunteers were randomized to receive placebo, lovastatin, or rhAPC before intrabronchial segmental endotoxin challenge. FDG-PET imaging was performed before and after endotoxin instillation. The rate of [(18)F]FDG uptake was calculated as the influx constant K(i) by Patlak graphical analysis. Bronchoalveolar lavage (BAL) was performed to determine leukocyte concentrations for correlation with the PET imaging results.Measurements and main resultsThere was a statistically significant decrease in K(i) in the lovastatin-treated group that was not seen in the placebo-treated group, suggesting attenuation of inflammation by lovastatin treatment despite a small decrease in BAL total leukocyte and neutrophil counts that was not statistically significant. No significant decrease in K(i) was observed in the rhAPC-treated group, correlating with a lack of change in BAL parameters and indicating no significant antiinflammatory effect with rhAPC.ConclusionsFDG-PET imaging is a sensitive method for quantifying the lung-specific response to antiinflammatory therapies and may serve as an attractive platform for assessing the efficacy of novel antiinflammatory therapies at early phases in the drug development process. Clinical trial registered with www.clinicaltrials.gov (NCT00741013).
| S-EPMC2742744 | biostudies-literature
Project description:Fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is widely used as positron-emission-tomography (PET) radiotracer for the detection and staging of human cancer. Tumor uptake of FDG varies substantially between different cancer types and between patients with the same tumor type. The molecular basis for this heterogeneity is unknown. Using cancer cell lines and primary human tumors of distinct histologic origins, we here show that increased FDG uptake is universally associated with coordinate upregulation of genes within the glycolysis, pentose-phosphate, and other related metabolic pathways. In primary human breast cancers, this FDG signature shows significant overlap with established breast cancer signatures for the “basal-like” disease subtype and “poor prognosis”. FDG high breast cancer showed significantly more gene copy number alterations genome wide than FDG low cancers. About 50 % of primary breast cancers with high FDG uptake and FDG gene expression signature show DNA copy gain encompassing the c-myc gene locus and express gene sets regulated by the transcription factor MYC. Our data shows that FDG-PET marks a distinct subset of “basal-like” human breast cancer which is characterized by MYC and prognostically unfavorable gene expression signatures, suggesting that FDG-PET imaging may be useful to risk-stratify patients with locally advanced breast cancer.
2011-11-01 | GSE21217 | GEO
Project description:We present an illustrative educational case series focused on the use of nuclear imaging in the diagnosis and follow-up of cardiac inflammation. (Level of Difficulty: Intermediate.) Graphical abstract
| S-EPMC9681667 | biostudies-literature
Project description:COPD and smoking are characterised by pulmonary inflammation. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging may improve knowledge of pulmonary inflammation in COPD patients and aid early development of novel therapies as an imaging biomarker. To evaluate pulmonary inflammation, assessed by FDG uptake, in whole and regional lung in "usual" (smoking-related) COPD patients, alpha-1 antitrypsin deficiency (α1ATD) COPD patients, smokers without COPD and never-smokers using FDG PET/CT. Secondly, to explore cross-sectional associations between FDG PET/CT and systemic inflammatory markers in COPD patients and repeatability of the technique in COPD patients. Data from two imaging studies were evaluated. Pulmonary FDG uptake (normalised Ki; nKi) was measured by Patlak graphical analysis in four subject groups: 84 COPD patients, 11 α1ATD-COPD patients, 12 smokers and 10 never-smokers. Within the COPD group, associations between nKi and systemic markers of inflammation were assessed. Repeatability was evaluated in 32 COPD patients comparing nKi values at baseline and at 4-month follow-up. COPD patients, α1ATD-COPD patients and smokers had increased whole lung FDG uptake (nKi) compared with never-smokers (0.0037±0.001, 0.0040±0.001, 0.0040±0.001 versus 0.0028±0.001 mL·cm-3·min-1, respectively, p<0.05 for all). Similar results were observed in upper and middle lung regions. In COPD participants, plasma fibrinogen was associated with whole lung nKi (β=0.30, p=0.02) in multivariate analysis adjusted for current smoking, forced expiratory volume in 1 s % predicted, systemic neutrophils and C-reactive protein levels. Mean percentage difference in nKi between the baseline and follow-up was 3.2%, and the within subject coefficient of variability was 7.7%. FDG PET/CT has potential as a noninvasive tool to enable whole lung and regional quantification of FDG uptake to assess smoking- and COPD-related pulmonary inflammation.
| S-EPMC8405867 | biostudies-literature
Project description:Positron emission tomography (PET) visualizes increased cellular [F]fluorodeoxyglucose ([F]FDG) uptake. Pulmonary hypertension (PH) is conceived of a proliferative disease of the lung vessels. Increased glucose uptake can be quantified as pulmonary [F]FDG uptake via PET imaging. Because the angioproliferative mechanisms in PH are still in need of further description, the aim of the present study was to investigate whether [F]FDG PET/CT imaging can elucidate these pathophysiologic mechanisms in different etiologies of PH.Patients (n?=?109) with end-stage pulmonary disease being evaluated for lung transplant were included in this observational study. Mean standardized uptake value (SUVmean) of predefined regions of interest in lung parenchyma (LP), left (LV), and right ventricle (RV) of the heart, and SUVmax in pulmonary artery (PA) were determined and normalized to liver uptake. These SUV ratios (SUVRs) were compared with results from right heart catheterization (mean pulmonary artery pressure [mPAP], pulmonary vascular resistance [PVR]), and serum N-terminal pro-brain natriuretic peptide. Group comparisons were performed and Pearson correlation coefficients (r) were calculated.The [F]FDG uptake ratios in LP, RV, RV/LV, and PA, but not in LV, were found to be significantly higher in both patients with mPAP ?25?mm Hg (P?=?0.013, P?=?0.006, P?=?0.049, P?=?0.002, P?=?0.68, respectively) and with PVR ?480?dyn·s/cm (P?<?0.001, P?=?0.045, P?<?0.001, P?<?0.001, P?=?0.26, respectively). The [F]FDG uptake in these regions positively correlated also with mPAP, PVR, and N-terminal pro-brain natriuretic peptide. The SUVR of PA positively correlated with the SUVR of LP and RV (r?=?0.55, r?=?0.42, respectively).Pulmonary and cardiac [F]FDG uptake in PET imaging positively correlated with the presence and severity of PH in patients with end-stage pulmonary disease. Increased glucose metabolism in the central PAs seems to play a certain role in terms of severity of PH. These results suggest that [F]FDG-PET imaging can help understand the pathophysiology of PH as a proliferative pulmonary disease.
| S-EPMC4998336 | biostudies-literature
Project description:Positron emission tomography (PET) is a nuclear medicine procedure based on the measurement of positron emission from radiolabelled tracer molecules. These radiotracers allow biologic processes to be measured and whole body images to be obtained which demonstrates sites of radiotracer accumulation. The most common radiotracer in use today is 18F-fluorodeoxyglucose (18F-FDG) which is a radiolabelled sugar (glucose) molecule. Imaging with 18F-FDG PET is used to determine sites of abnormal glucose metabolism and can be used to characterize and localize many types of tumours.
Cancer treatment and outcome depend largely on the accurate diagnosis and staging of disease. There is extensive data in the literature indicating the importance of FDG-PET imaging in accurately characterizing disease, as well as determining stage and sites of recurrent disease in many cancer types. For these indications, functional imaging with PET provides unique information which is not available from standard medical imaging modalities such as ultrasound, X-ray, computerized tomography (CT) or magnetic resonance imaging (MRI).
The objectives of this study are to document the safety and efficacy of 18F-FDG produced by the British Columbia Cancer Agency (BCCA) at its Tri-University Meson Facility (TRIUMF) production facility and to evaluate FDG-PET as a diagnostic and decision making tool in the management of oncology patients in British Columbia. With a population base of over 4 million people, standardized cancer treatment protocols, and evidence based guidelines for FDG-PET imaging, the BCCA is positioned to make an important contribution to defining the role of PET in the Canadian health care system.
| 2020046 | ecrin-mdr-crc
Project description:ObjectivesTo investigate fused multiparametric positron emission tomography/magnetic resonance imaging (MP PET/MRI) at 3T in patients with locally advanced cervical cancer, using high-resolution T2-weighted, contrast-enhanced MRI (CE-MRI), diffusion-weighted imaging (DWI), and the radiotracers [18F]fluorodeoxyglucose ([18F]FDG) and [18F]fluoromisonidazol ([18F]FMISO) for the non-invasive detection of tumor heterogeneity for an improved planning of chemo-radiation therapy (CRT).Materials and methodsSixteen patients with locally advanced cervix were enrolled in this IRB approved and were examined with fused MP [18F]FDG/ [18F]FMISO PET/MRI and in eleven patients complete data sets were acquired. MP PET/MRI was assessed for tumor volume, enhancement (EH)-kinetics, diffusivity, and [18F]FDG/ [18F]FMISO-avidity. Descriptive statistics and voxel-by-voxel analysis of MRI and PET parameters were performed. Correlations were assessed using multiple correlation analysis.ResultsAll tumors displayed imaging parameters concordant with cervix cancer, i.e. type II/III EH-kinetics, restricted diffusivity (median ADC 0.80x10-3mm2/sec), [18F]FDG- (median SUVmax16.2) and [18F]FMISO-avidity (median SUVmax3.1). In all patients, [18F]FMISO PET identified the hypoxic tumor subvolume, which was independent of tumor volume. A voxel-by-voxel analysis revealed only weak correlations between the MRI and PET parameters (0.05-0.22), indicating that each individual parameter yields independent information and the presence of tumor heterogeneity.ConclusionMP [18F]FDG/ [18F]FMISO PET/MRI in patients with cervical cancer facilitates the acquisition of independent predictive and prognostic imaging parameters. MP [18F]FDG/ [18F]FMISO PET/MRI enables insights into tumor biology on multiple levels and provides information on tumor heterogeneity, which has the potential to improve the planning of CRT.
| S-EPMC4864307 | biostudies-literature