2-deoxyglucose Research Articles

Prognostic value of pretreatment 18F-FDG PET/CT imaging metabolic parameters in patients with early-stage extranodal natural killer/T cell lymphoma

Objective To investigate the prognostic value of metabolic parameters calculated from pretreatment 18F-fluorodeoxyglucose (FDG) PET/CT images in patients with extranodal natural killer/T cell lymphoma (ENKTL) of stage Ⅰ-Ⅱ. Methods From August 2010 to April 2018, 67 patients with ENKTL of stage Ⅰ-Ⅱ disease (47 males, 20 females; median age 57 years) in the First Affiliated Hospital of Nanjing Medical University were enrolled, and the clinic data and pretreatment 18F-FDG PET/CT imaging data were retrospectively analyzed. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of tumor tissue were calculated from PET/CT images with the threshold value of 40% of maximum standardized uptake value (SUVmax). The optimal cut-off values of progression-free survival (PFS) and overall survival (OS) of SUVmax, MTV and TLG were investigated by using receiver operating characteristic (ROC) curve analysis. Kaplan-Meier method, log-rank test and Cox proportional hazards model were used for data analysis. Results SUVmax, MTV and TLG of 67 patients were 12.32(8.65, 16.96), 13.13(7.37, 22.74) ml, 92.17(46.54, 198.46), respectively. ROC curve analysis showed that the cut-off values of SUVmax, MTV and TLG were 13.09, 18.05 ml and 152.81, respectively. Univariate analysis showed that B symptoms, lactate dehydrogenase (LDH) level, β2-microglobulin, Eastern Cooperative Oncology Group (ECOG) score, Korean prognostic index (KPI), SUVmax, MTV, TLG and treatment mode (chemotherapy or chemoradiotherapy) were relative factors affecting PFS (χ2: 5.466-27.163, all P 0.05). Multivariate analysis showed that ECOG score, MTV and TLG were independent prognostic predictors of PFS (relative ratio (RR): 5.107-6.802, all P<0.05), and ECOG score, MTV, TLG and treatment mode were independent prognostic predictors of OS (RR: 0.221-9.106, all P<0.05). Conclusions MTV and TLG from pretreatment 18F-FDG PET/CT images are independent prognostic factors for PFS and OS in patients with ENKTL of stage Ⅰ-Ⅱ. MTV and TLG may be more useful than SUVmax for prognosis. Key words: Lymphoma, extranodal NK-T cell; Positron-emission tomography; Tomography, X-ray computed; Deoxyglucose

Combination of Magnetic Resonance Imaging and 18-Fluoro Deoxy Glucose Positron Emission Tomography in Functional Imaging of Medium to Large Asymptomatic Abdominal Aortic Aneurysms

Combination of Magnetic Resonance Imaging and 18-Fluoro Deoxy Glucose Positron Emission Tomography in Functional Imaging of Medium to Large Asymptomatic Abdominal Aortic Aneurysms

Predictive value of 18F-FDG PET conventional parameters and radiomics features for invasive breast cancer patients with uncertain HER2 expression by immunohistochemistry

Objective To explore the predictive value of 18F-fluorodeoxyglucose (FDG) PET conventional parameters and radiomics features for human epidermal growth factor receptor 2 (HER2) expression which was uncertain by immunohistochemistry (IHC) detection in invasive breast cancer. Methods From April 2012 to December 2017, 76 patients (all were females, age: (50.8±10.9) years) with invasive breast cancer and with uncertain HER2 expression by IHC in Tianjin Medical University Cancer Institute and Hospital were enrolled retrospectively. The 18F-FDG PET/CT images before treatment were reviewed and the expression of HER2 were confirmed by fluorescence in situ hybridization (FISH). The tumor lesions were manually outlined, and the radiomics features from PET images were extracted. Wilcoxon test was used to determine whether there was difference in PET conventional metabolic parameters (maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG)) and radiomics features between HER2-negative and HER2-positive groups. The receiver operating characteristic (ROC) curve analysis was used to compare the predictive efficacy of PET radiomics features for HER2 expression. Results There were 41 HER2-positive patients and 35 HER2-negative patients. No significant differences in PET conventional metabolic parameters between different HER2 expression groups were observed (U values: from -1.598 to 1.551, all P>0.05). A total of 38 PET radiomics features were extracted, and there were significant differences in gray mean, correlation, contrast, inertia, and inverse different moments between 2 groups(U values: from -2.413 to 2.527, all P<0.05). The area under the curve of the above 5 parameters for prediction of HER2 expression were 0.643, 0.638, 0.647, 0.644 and 0.643, respectively, and the contrast was the best parameter. Conclusions PET radiomics features can effectively identify HER2 expression in patients with invasive breast cancer to some extent, and the contrast may be the best. Conventional metabolic parameters have limited predictive value. Key words: Breast neoplasms; Receptor, epidermal growth factor; Immunohistochemistry; Positron-emission tomography; Tomography, X-ray computed; Deoxyglucose; Radiomics

Activated but Not Quiescent Hematopoietic Stem Cells Rely Readily on Glycolysis As Their Main Source of Energy

Elucidating mechanisms that regulate hematopoietic stem cells (HSCs) quiescence is critical for improving bone marrow transplantation. It is postulated that quiescent HSCs rely mostly on glycolysis rather than mitochondrial oxidative phosphorylation (OXPHOS) as their energy source. We have identified a population of HSCs with low mitochondrial activity (LSKCD150+CD48- within the 25% lowest mitochondrial membrane potential; MMP-low) that we show are highly enriched in quiescent HSCs (~95% ±2.65 in G0) as measured by pyronin Y/Hoechst staining in contrast to LSKCD150+CD48- within 25% highest MMP (MMP-high) that are in majority in G1/S/G2/M phase of cell cycle (55.4%±16; p&amp;lt;0.05; n=3). MMP-low HSCs exhibit greater in vivo competitive repopulation ability (3.7 fold; p=0.021; n=10 mice) at 16 weeks as compared to MMP-high fractions, show higher self renewal ability and are enriched in label-retaining H2B-GFP+ cells (~3 fold; p&amp;lt;0.01; n=3). Conversely, label-retaining GFP+HSCs maintain lower MMP than non-label-retaining cells. Altogether these results reinforce the notion that MMP-low HSCs are quiescent whereas MMP-high HSCs are primed/activated. Using single cell RNA-sequencing (scRNA-seq) analysis to interrogate the transcriptome by a Fluidigm C1 platform within MMP-high versus MMP-low HSCs we found major metabolic pathways including OXPHOS, exhibit significantly greater expression within the MMP-high than in the MMP-low HSC fraction. Seahorse analysis confirmed that MMP-high but not -low hematopoietic stem and progenitor cells (HSPCs) use OXPHOS as their source of energy (3.9 fold; n=16 mice). Unexpectedly, glycolytic gene expression was also enriched in the primed MMP-high HSCs and relatively low in quiescent MMP-low HSCs. qRT-PCR analysis further confirmed that the expression of glycolytic enzymes and other genes including glucose transporter 1 (Glut1, slc2a1) that is the main glucose transporter on HSCs is greater in MMP-high relative to -low HSCs. These unforeseen findings raised the potential that despite the current consensus in HSC biology, glycolysis may more readily support activated rather than quiescent HSCs. We thus measured the glucose uptake in MMP-low vs -high HSCs under metabolic (pyruvate, glucose and glutamine)-restricted conditions. Using 2NBDG, a fluorescently tagged glucose analog, we found that MMP-high HSCs uptake 3.3-fold more glucose and contained three times more 2NBDG+ cells as compared to MMP-low HSCs (p&amp;lt;0.001 for each; n=3). Pharmacological inhibition of Glut1 reduced glucose uptake in MMP-high but not -low HSCs suggesting the specific sensitivity of MMP-high HSCs to the glucose inhibition. In addition, activation of tricarboxylic acid cycle TCA cycle with combined methyl-pyruvate and dimethyl-alpha-ketoglutarate led to a greater glucose uptake (~3.5 fold) in MMP-high as compared to MMP low HSCs (~2.2 fold; p&amp;lt;0.0001). To address the degree to which glycolysis is necessary, FACS-purified MMP-low and -high HSCs were incubated with 2-Deoxy D-Glucose (2DG) - a glucose analog - that inhibits glycolysis via its action on hexokinase. While glucose deprivation with 50 mM dose of 2DG within 12 hours did not have much effect on MMP-low HSCs, over 60% of MMP-high HSCs died (p&amp;lt;0.001; n=3), suggesting that MMP-high but not -low HSCs rely readily on glycolysis for their survival. Also, the inhibition of mitochondrial transport of pyruvate that is the end product of glycolysis (α-cyano-4-hydroxycinnamate (CHC)), decreased survival in MMP-high HSCs by 80% with negligible effect on MMP-low HSCs (p&amp;lt;0.01; n=3). Finally 50 FACS-purified HSCs (LSKCD150+CD48-MMP-low or -high) were transplanted in lethally irradiated mice along with 200,000 unfractionated bone marrow cells in a competitive repopulation assay and mice were subsequently treated with 2DG or control vehicle every other day for two weeks. Two months later, 2DG treatment led to significantly enhanced reconstitution levels in MMP-high HSCs with no or little effect on MMP low reconstitution levels (ongoing). These combined results suggest that primed MMP-high rather than quiescent MMP-low HSCs rely on glycolysis as their main source of energy. These findings are consistent with the concept that glycolysis is key in sustaining rapidly dividing cells such as embryonic stem cells and cancer cells. Disclosures Ghaffari: Rubius Therapeutics: Consultancy.

Application value of 18F-FDG PET/CT in predicting EGFR mutation status in non-small cell lung cancer

Lung cancer is a malignant tumor with the high morbidity and mortality in the world, and non-small cell lung cancer (NSCLC) is the most common type. The emergence of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in recent years has provided new treatment option for NSCLC patients. The efficacy of EGFR-TKI is closely related to the EGFR mutation status, but the current detection methods for gene mutation have certain limitations. As a non-invasive method, 18F-fluorodeoxyglucose (FDG) PET/CT shows a certain potential in the detection of EGFR gene mutation status. In this paper, the recent research and progress of PET/CT in predicting the mutation status of EGFR gene are reviewed. Key words: Carcinoma, non-small-cell lung; Mutation; Receptor, epidermal growth factor; Positron-emission tomography; Tomography, X-ray computed; Deoxyglucose; Trends

Efficient graph cut optimization using hybrid kernel functions for segmentation of FDG uptakes in fused PET/CT images

The purpose of this work is to segment the multi region Fluoro Deoxy Glucose radioactivity uptakes from fused Positron Emission Tomography / Computerized Tomography images automatically irrespective of their location in the body. Color image processing is performed to filter and enhance the saturation components of the images. The proposed method of graph cut image partitioning through kernel mapping of the image data is applied for the saturation equalized components of Red, Green, and Blue model images. Energy minimization of the objective function includes the data term minimization within each segmentation region and smoothening the regularization term preserving the boundary regions. Hybrid kernel functions are used for partitioning by graph-cut iterations and computation of region parameters through fixed-point computation. This method combines the performance of global and local kernel functions which makes the segmentation robust and accurate. The performance assessment is carried out for different views of fused Positron Emission Tomography / Computerized Tomography images, and are evaluated qualitatively, quantitatively, and comparatively. This method can be applied for the analysis of certain image features, diagnosis, and display purposes.

Value of 18F-FDG PET/CT in the diagnosis and treatment of colorectal cancer liver metastases

18F-fluorodeoxyglucose (FDG) PET/CT offers excellent diagnostic performance on colorectal cancer liver metastases(CRCLM) in terms of sensitivity and specificity, and can comprehensively identify the presence of extrahepatic metastases and provide valuable information for the treatment decision making. 18F-FDG PET/CT can also be used in the early assessment of response to CRCLM therapy and survival prediction. However, the diagnostic value of PET/CT is limited for lesions with diameter within 10 mm or with activity inhibited strongly by chemotherapy. PET combined with contrast enhanced CT may have potential value in improving diagnostic sensitivity for CRCLM. Key words: Colorectal neoplasms; Neoplasm metastasis; Liver; Positron-emission tomography; Tomography, X-ray computed; Deoxyglucose

Diagnosis of primary osseous malignant tumors with 18F-FDG PET/CT in patients over 40 years old

Objective To investigate the value of 18F-fluorodeoxyglucose (FDG) PET/CT in the diagnosis of different pathological types of primary osseous malignant tumors (POMT) in patients over 40 years old. Methods Fifty-two patients (30 males, 22 females, median age: 60(41-81)years) with POMT who underwent 18F-FDG PET/CT and were pathologically confirmed from January 2013 to May 2018 in Cancer Hospital of Tianjin Medical University were reviewed. The region of interest was drawn and the standardized uptake value (SUV) was automatically measured. The SUV in different pathological types of POMT was compared using one-way analysis of variance or two-sample t test. Results The 52 POMT included 22 sarcomas, 16 isolated myelomas (IM), and 14 primary bone lymphomas (PBL). The SUV in PBL was significantly higher that than in sarcomas and IM with the maximum SUV (SUVmax) of 21.6±12.4, 13.5±7.7 and 9.0±6.4 respectively(F=7.56, P<0.01), and the mean SUV (SUVmean) of 12.9±7.8, 7.5±4.5, and 5.6±4.4, respectively(F=6.92, P<0.01). In the sarcoma group, the SUV of undifferentiated sarcomas was significantly higher than that of other well-differentiated sarcomas (SUVmax: 21.1±5.4 vs 11.3±6.9, SUVmean: 11.8±3.3 vs 6.3±4.1; t=-2.92, -2.71, both P<0.01). The growth pattern of sarcomas and IM was different on CT images. Conclusions The FDG uptake of PBL is higher than that of other pathological types. CT features are helpful for the differential diagnosis of POMT in 18F-FDG PET/CT. Key words: Bone neoplasms; Middle aged; Aged; Positron-emission tomography; Tomography, X-ray computed; Deoxyglucose

In vivo and in vitro evaluation of 177Lu-labeled DOTA-2-deoxy-D-glucose in mice. A novel radiopharmaceutical agent for cells imaging and therapy.

Incorporation of lutetium-177 (177Lu) into suitable molecules that are implicated in cancer pathology represents a promising approach for the diagnosis and treatment of cancer. The goal of the present study was to develop a novel 177Lu labeled radiopharmaceutical agent for both radioimaging and targeted radionuclide therapy. Given the synthetic versatility of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) ligand as a metal chelator and high demand of sugar molecules such as deoxyglucose (DG) in cancer cells, we carried out the radiosynthesis of a novel radiopharmaceutical agent, namely, 177Lu-DOTA-DG, and utilized it for imaging of cancer and also for the targeted radiation therapy of cancer tissues. In this study, we developed an efficient radiochemical synthesis of 177Lu-DOTA-DG and evaluated its pharmacological properties in vitro/in vivo. Our results showed DOTA-DG can be labeled with 177Lu with excellent radiochemical yield at 90oC in 30min. The resulting 177Lu-DOTA-DG exhibited high degree of stability without significant radiolysis up to 120h in human serum and phosphate buffer. Favorable pharmacokinetics profile was demonstrated by rapid blood clearance in 4T1 murine tumor mice and heterogeneous whole body biodistribution of 177Lu-DOTA-DG. Further, Comet assay experiments indicated that cancer cells treated with 177Lu-DOTA-DG showed significant higher degree of DNA damage compared to cells treated with 177Lu3+ or non-treated cells. This study showed that there is a great potential of using 177Lu-DOTA-DG as an imaging and therapeutic agent for cancer diagnosis and treatment. Furthermore, this study provides valuable information for developing novel 177Lu-labeled radiopharmaceuticals.

Correlations between striatal dopamine transporter distribution, glucose metabolism and clinical symptoms in Parkinson′s disease

Objective To investigate the correlations among striatal dopamine transporter (DAT) distribution, glucose metabolism and Parkinson′s disease (PD) clinical symptoms. Methods Twenty-five clinically confirmed idiopathic PD patients (17 males, 8 females, age: (59.8±9.2) years) who underwent 11C-2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane (CFT) and 18F-fluorodeoxyglucose (FDG) PET imaging from January 2015 to December 2016 were reviewed. The detailed clinical scores were systematically collected from all patients. Correlations between DAT distribution, glucose metabolism and clinical symptoms were evaluated at global and voxel levels using Pearson correlation analysis. Results There were significantly positive correlations between the PD-related pattern (PDRP) value and unified PD rating scale (UPDRS) motor scores, non-motor symptoms scale (NMSS) scores, activity of daily living scale (ADL) scores (r values: 0.580, 0.522, 0.557, all P 0.05). The CFT uptake of ipsilateral caudate nucleus and anterior putamen were negatively correlated with ADL scores (r values: -0.502, -0.522, both P 0.05). The presence of the significant correlations between UPDRS motor scores, ADL scores and the CFT radioactive count were confirmed in left caudate nucleus and left putamen (r values: from -0.90 to -0.47, all P<0.05). The metabolic PET imaging disclosed a set of brain regions correlating with the clinical symptoms. The presence of significant correlations between the metabolic PET imaging and CFT uptake were confirmed in bilateral caudate nucleus (r values: 0.47-0.90, both P<0.01), precentral gyrus and insula (r values: -0.90 to -0.47, all P<0.01). Conclusion The correlations between DAT distribution, glucose metabolism and PD clinical symptoms are complicated, which promote the understanding in the proper application of dopaminergic and metabolic PET imaging in PD and offer more evidences in PD pathophysiological mechanisms. Key words: Parkinson disease; Dopamine plasma membrane transport proteins; Signs and symptoms; Positron-emission computed; Deoxyglucose

Differential diagnosis value of single-case statistical parametric mapping analysis with 18F-FDG PET imaging for Parkinsonism

Objective To investigate the value of statistical parametric mapping (SPM) analysis of 18F-fluorodeoxyglucose (FDG) PET imaging in the differential diagnosis of Parkinsonism in single-case level. Methods SPM software was used to retrospectively analyze the 18F-FDG PET images of 160 patients (104 males, 56 females, age: 30-82 years) who were suspected with Parkinsonism at baseline and were clinical confirmed by follow-up from April 2010 to December 2017. 18F-FDG PET images of patients was compared with those of age-matched healthy controls in single-case level using two-sample t test in SPM software to obtain the imaging diagnosis. By comparing imaging diagnosis with the final clinical diagnosis, the diagnostic accuracy of SPM in the overall cohort as well as the early subcohort (duration of disease less than 2 years (56 males, 22 females, age: 50-82 years)) were calculated respectively. Results Among 160 patients with Parkinsonism, 146(91.2%) had the same 18F-FDG PET diagnosis as their final clinical diagnosis. The diagnostic sensitivity for Parkinson′s disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and cortical basal ganglia degeneration (CBD) were 93.5%(86/92), 92.3%(24/26), 84.0%(21/25) and 15/17, respectively. The specificity were 95.6%(65/68), 95.5%(128/134), 96.3%(130/135) and 100%(143/143), respectively. In the early subcohort, the analysis also achieved similar differential diagnosis effectiveness(92.3%). Conclusion The single-case 18F-FDG PET imaging SPM analysis can be helpful in the early differential diagnosis of Parkinsonism effectively. Key words: Parkinsonian disorders; Positron-emission tomography; Diagnosis, differential; Deoxyglucose

Metabolic patterns of 11C-CFT and 18F-FDG PET/CT imaging in tremor and non-tremor Parkinson′s disease

Objective To investigate the metabolic patterns of 11C-2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane (CFT) and 18F-fluorodeoxyglucose (FDG) PET/CT imaging in patients with tremor and non-tremor Parkinson′s disease (PD). Methods From March 2018 to March 2019, 28 PD patients (19 tremor patients: 14 males and 5 females, age: (59.9±11.4) years; 9 non-tremor patients: 3 males and 6 females, age: (62.6±9.0) years) were enrolled. For the two groups, the 11C-CFT uptake values in caudate nucleus, anterior putamen and posterior putamen as well as 18F-FDG uptake values in all brain regions were calculated by regions of interest (ROI) method. Two-sample t test or Mann-Whitney u test were used to analyze the data. Results Caudate nucleus 11C-CFT uptake in PD patients with tremor was higher than that without tremor (3.03±0.51 vs 2.60±0.62; t=2.687, P<0.05). Yet thalamus glucose uptake of non-tremor PD patients showed more active than tremor patients (1.14±0.05 vs 1.10±0.03; t=3.449, P<0.01). Sorted by modified Hoehn-Yahr stage, tremor patients in advanced stage (stage≥2.5) were characterized by glucose uptake increase in the putamen and cerebellum compared with non-tremor advanced group (1.27±0.04 vs 1.21±0.05, 0.94±0.04 vs 0.86±0.08; t values: 2.695 and 2.492, both P<0.05). Metabolic decrease in the premotor areas was observed in tremor patients in advanced stage compared with early stage (1.07±0.02 vs 1.10±0.03; t=2.053, P<0.05). Conclusion 11C-CFT and 18F-FDG PET/CT imaging can indicate different metabolic patterns between tremor and non-tremor PD, thus providing information for clinical practice and differential diagnosis. Key words: Parkinson disease; Tremor; Positron-emission tomography; Tomography, X-ray computed; Tropanes; Deoxyglucose

Correlation and differential diagnostic value of 18F-FDG imaging and arterial spin labeling cerebral perfusion imaging acquired by synchronous PET/MR in Parkinsonism

Objective To discuss the correlation between 18F-fluorodeoxyglucose (FDG) imaging and arterial spin labeling perfusion weighted imaging (ASL-PWI) using synchronous PET/MR, and explore the feasibility of 18F-FDG PET and ASL for differential diagnosis in Parkinsonism (PS). Methods A retrospective analysis was performed in 24 patients with Parkinson′s disease (PD), 10 patients with multiple system atrophy (MSA) and 6 patients with progressive supranuclear palsy (PSP) who all underwent 18F-FDG PET/MR imaging from October 2017 to December 2018 (15 males, 25 females, age: 34-77 years). Synchronously acquired data, including MRI T1, 18F-FDG PET and three dimensional (3D) ASL-PWI were extracted. T1 structure image was used to register with standard brain template, and the personalized brain template of each patient was obtained. Then, the templates were matched to the corresponding PET and ASL-PWI images, and the mean standardized uptake value (SUVmean) and mean cerebral blood flow (CBFmean) of each brain region could be extracted. Pearson correlation analysis was used to evaluate the correlation between SUVmean and CBFmean of the whole brain and the regions of interest (ROI; caudate nucleus, putamen, midbrain, pons and cerebellum). One-way analysis of variance and least significant difference t test were used to evaluate the characteristics of SUVmean and CBFmean in different diagnostic groups. The diagnostic values of SUVmean and CBFmean in different ROI were evaluated with receiver operating characteristic (ROC) curve analysis. Results A total of 2 800 pairs of SUVmean and CBFmean were obtained from 40 cases in 3 groups. The overall correlation between them was good (r=0.468, P<0.01). There were also significant correlations between SUVmean and CBFmean in caudate nucleus, putamen, pons and cerebellum (r values: 0.346-0.492, all P<0.05). The CBFmean of cerebellum in MSA group was significantly lower than that in PD group ((36.92±11.35) vs (47.92±10.75) ml·100 g-1·min-1;F=4.817, t=2.675, P<0.05). Compared to the PSP group, CBFmean in caudate nucleus was higher in PD group ((30.02±3.51) vs (40.21±8.13) ml·100 g-1·min-1;F=5.393, t=2.969, P<0.05). The similar results were obtained for SUVmean. To differentiate PD with MSA, CBFmean of cerebellum possessed the highest diagnostic efficiency, with the area under ROC curve (AUC), sensitivity and specificity reaching 0.792, 83.3% and 70.0% respectively. To differentiate PSP with PD or MSA, CBFmean in caudate nucleus had the highest diagnostic efficiency, and the AUC were 0.903 and 0.933 respectively. Conclusions In patients with PD, MSA and PSP, the level of 18F-FDG glucose metabolism is in good agreement with the ASL cerebral blood flow perfusion obtained by synchronous PET/MR. The distribution characteristics of specific ROI in both PET and MR imaging can be helpful to the differential diagnosis of PS. Key words: Parkinsonian disorders; Positron-emission tomography; Magnetic resonance imaging; Diagnosis, differential; Deoxyglucose

Effect of butein and glucose on oxidative stress and p38 activation marker in non-small cell lung cancer cell.

Tumor microenvironment is known to alter the anticancer drug efficiency. One of the factors that get altered in cancer microenvironment is glucose concentration. Butein, an active principle from plant, known to have anticancer effect against different types of tumor. The objective of the study is to determine the effect of butein on glucose exposed non-small cell lung cancer cells (NSCLCCs). The current study deals with the effect of butein (6.25-50μM) on NSCLCCs treated with different concentrations (0-40 mM) of glucose. Glucose concentration, 0 mM and 40 mM, was found to be lethal at 72 h. Viable cell numbers were statistically increased in 5-mM, 10-mM, and 20-mM glucose-treated cells. Butein at 12.5 µM inhibits (p < 0.05) glucose-induced cell proliferation. Butein inhibits glucose-induced proliferation through DNA damage and oxidative stress. Mitochondrial reactive oxygen species (ROS) level was elevated in 20-mM glucose-treated cells when compared to 5-mM glucose-treated cells, whereas butein treatment further increases glucose-induced mitochondrial ROS. Pharmacological inhibitor of glycolysis, such as 2-deoxy glucose (2-DG), was found to inhibit (p < 0.05) glucose-induced cells proliferation. Furthermore, 2-DG and butein showed synergistic anticancer effect. Butein treatment increases p38 phosphorylation. Inhibition of p38 phosphorylation and antioxidant pretreatment partially revert the glucose-induced cell proliferation. However, inhibition of p38 phosphorylation combined with antioxidant pretreatment completely reverts the anticancer effect of butein. The present study concludes through the evidence that butein could serve as a potential anticancer compound in tumor microenvironment.

Mitochondrial DNA depletion and clinical presentations

Transcatheter aortic valve replacement (TAVR) is a paradigm shift for the management of severe symptomatic aortic stenosis. Infective endocarditis is a dreaded complication, which may potentially occur with TAVR, in a similar fashion to surgical aortic valve prostheses. TAVR infective endocarditis (TAVR-IE) may often be under recognized; therefore, it may be associated with higher morbidity and mortality. Here, we describe the difficulties faced with the diagnosis of TAVR-IE, and elucidate the microbiological profiles, various diagnostic strategies, and management options. Diagnosis of TAVR-IE is challenging, with potentially a lower yield on echocardiography. There is an expanding body of literature on the roles of advanced cardiac imaging techniques such as multidetector cardiac computed tomography (MDCT), Fluoro Deoxy Glucose Positron Emission Tomography (FDG-PET) and labeled leukocyte scintigraphy. Management of these patients should occur in a tertiary care hospital, by a dedicated multi-disciplinary heart valve infective endocarditis team, with the availability for advanced cardiac interventional and surgical procedures. Finally, we analyze the gaps in guidelines for management of prosthetic valve endocarditis in TAVR patients.

Manejo Quirúrgico del Carcinoma Metastásico de Primario Desconocido de Cabeza y Cuello

Propósito de la revisión: el objetivo de la revisión es delinear el rol del Manejo Quirúrgico del carcinoma metastásico primario de cabeza y cuello. Buscamos reportes en indicaciones, posibles hallazgos y subsecuentes tratamientos.&#x0D; Recientes hallazgos: La punción aspirativa con aguja fina, permite diferenciar la etiología de los nódulos del cuello: melanoma, carcinoma tiroideo, linfoma y otros tumores indiferenciados. La medición de tiroglobulina ayuda a diferenciar una neoplasia de tiroides. El nivel ganglionar afectado I al III incluye el protocolo de paratiroidectomia, amigadalectomía. El nivel ganglionar IV y V el primario es infraclavicular.&#x0D; Extracto: El cáncer metastásico de primario oculto es una neoplasia con confirmación histológica pero con lesión primaria desconocida. Su manejo es controversial y en la mayoría de los casos insuficiente para llegar al diagnóstico, incluso con la autopsia. La aproximación inicial comprende una serie de exámenes de laboratorio e imágenes de alta complejidad que incluyen la tomografía por emisión de positrones con el test de la Flúor 2-Deoxi Glucosa (FDG-PET/CT), los estudios de anatomía patológica son el segundo paso dentro del manejo estándar e incluyen la Punción y Aspiración con Aguja fina (PAAF). La microscopia tradicional no es suficiente para identificar el tumor primario, las tinciones inmunohistoquímicas aunque no son especificas ni sensibles ayudan con ese propósito y aún más la microscopia electrónica. La biopsia o procedimientos más agresivos como la amigdalectomía son conductas a seguir si aún no se ha logrado el diagnóstico. Se presenta una revisión del estado del arte del manejo del Carcinoma Metastásico de Primario Desconocido de Cabeza y Cuello.

Value of 18F-FDG PET/CT in diagnosis of prosthetic vascular graft infection after endovascular aortic repair

Objective To study the features and clinical value of 18F-fluorodeoxyglucose (FDG) PET/CT in prosthetic vascular graft infections (PVGIs) after endovascular aortic repair (EVAR). Methods Data of 27 patients (22 males and 5 females, age range: 21-77 years, average age: 42 years) who underwent PET/CT imaging after EVAR from October 2011 to January 2017 were studied retrospectively. A total of 11 cases were finally diagnosed as PVGIs (PVGIs group), and the remaining 16 cases were defined as the negative group. PET/CT imaging features were compared between two groups. The detection rates of PET/CT and aortic CT angiography (CTA) for PVGIs were calculated and compared. Two-sample t test and Fisher exact test were used for data analysis. Results Significant uptake of FDG around the stents was detected by PET/CT in all patients in PVGIs group. The maximum standardized uptake value (SUVmax ) of 11 patients in early imaging was 14.9±3.3 (10.8-21.8) and that of 9 patients in delayed imaging was 13.8±3.4 (10.6-19.1). Six patients of the negative group underwent the delayed imaging. No uptake or mild uptake of FDG around the stents was observed in negative group, with the SUVmax of 1.7±0.8(1.0-2.9) in early imaging and 1.6±0.7(1.1-2.5) in delayed imaging. SUVmax in negative group was significantly lower than that in PVGIs group (t values: 12.6 and 11.8, both P<0.001). Five patients in PVGIs group were diagnosed as graft infections by the aortic CTA, while the remaining 6 cases showed no definitive infection signs on aortic CTA. The detection rate of aortic CTA was 5/11, which was significantly lower than that of PET/CT (P<0.05). In negative group, 6 patients had abnormal FDG uptakes in other areas and were finally confirmed as infectious lesions (n=3) or malignant tumors (n=3). Conclusion Compared with aortic CTA, 18F-FDG PET/CT is more sensitive and accurate in detection and diagnosis of PVGIs after EVAR. Key words: Aortic disease; Surgical procedures, operative; Blood vessel prosthesis; Infection; Positron-emission tomography; Tomography, X-ray computed; Deoxyglucose

Imaging features of 18F-FDG PET/CT in patients with autoimmune encephalitis

Objective To study the imaging features of 18F-fluorodeoxyglucose(FDG) PET/CT in patients with autoimmune encephalitis (AE) and evaluate the value of PET/CT on early diagnosis of AE. Methods Sixteen patients with AE (11 males, 5 females, age: 11-68 years) between March 2012 and December 2017 were included. Patients had positive antibodies in cerebrospinal fluid or (and) serum without immunity therapy. The imaging (18F-FDG PET/CT, MRI) and clinical data were analyzed. Results Nine patients suffered from anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and other 7 patients had limbic encephalitis (LE), which including 2 cases of anti-leucine-rich glioma inactivated 1(LGI1) encephalitis, 3 cases of anti-γ-aminobutyric acid-B receptor(GABABR) encephalitis, 1 case of anti-Hu encephalitis and 1 case of anti-Yo encephalitis. Fifteen patients showed scattered hypermetabolism or hypometabolism in the brain on PET/CT imaging, and the positive rate was 15/16. Among those patients with anti-NMDAR encephalitis, hypermetabolism in frontotemporal parietal lobes and hypometabolism in occipital lobe were shown; hypermetabolism in limbic systems including temporal lobe and hippocampus were shown in LE. No abnormal CT density was found at the same phase. Slightly higher signals on T2, fluid-attenuated inversion recovery (FLAIR) and diffusion weighted imaging (DWI) were detected in some patients, and the positive rate was 7/16. Conclusions Patients with AE of different types have different characteristics on 18F-FDG PET/CT. 18F-FDG PET/CT has high positive rate for early diagnosis of AE. Key words: Encephalitis; Autoimmune diseases; Positron-emission tomography; Tomography, X-ray computed; Deoxyglucose

Comparison of continuous bed motion and step-and-shoot acquisition modes in 18F-FDG PET/CT imaging

Objective To investigate the differences of acquisition protocols from continuous bed motion (CBM) and step-and-shoot (SS) modes and to observe their effects on image quality and standard uptake value (SUV) in 18F-fluorodeoxyglucose (FDG) PET/CT. Methods A total of 30 patients (13 males, 17 females; 40-71 years) who underwent 18F-FDG PET/CT from June 2017 to September 2017 were selected. Simulated acquisition protocols for a specific range (upper margin of the skull to the lower edge of sciatic bone) were established with CBM and SS modes. The differences between 2 modes for actual length requiring for a specific acquisition range and the differences in CT radiation dose were compared. Real PET/CT scans were performed using CBM and SS modes consecutively, and the differences in image quality and SUV were compared. Paired t test and χ2 test were used to analyze the data. Results For the specific acquisition range, the average acquisition length of CBM was reduced by 6.65% ((87.11±3.78) vs (93.32±6.02) cm; t=-7.737, P 0.05). The SUVmax of leg muscles at the end of the image was significantly higher in SS than that in CBM (1.24±0.53 vs 1.06±0.42; t=3.450, P 0.05). There were 73.33%(22/30) patients had images with overall high quality during SS and the percentage was 80.00%(24/30) during CBM (χ2=0.373, P>0.05). The percentage of patients with images of high quality at the end was 16.67%(5/30) during SS, which was significantly less than that during CBM (63.33%, 19/30; χ2=13.611, P<0.001). Conclusions For the specific acquisition range, CBM can reduce unnecessary CT scan range and radiation dose compared with SS. There is no significant difference in image quality and SUV from normal tissue and lesion except for the end of the image. Key words: Photon-emission tomography; Tomography, X-ray computed; Image processing, computer-assisted; Motion; Deoxyglucose

Clinical value of 18F-FDG PET/CT imaging in evaluation of antineutrophil cytoplasmic antibody-associated vasculitis

Objective To explore the clinical value of 18F-fluorodeoxyglucose (FDG) PET/CT in assessing antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods Fifteen patients(7 males, 8 females, age (66±11) years) with AAV between January 2015 and June 2017 were retrospectively analyzed. There were 6 patients diagnosed as granulomatosis with polyangiitis (GPA), 7 diagnosed as microscopic polyangiitis (MPA) and 2 diagnosed as eosinophilic granulomatosis with polyangiitis (EGPA). All patients underwent 18F-FDG PET/CT and the image features were observed and analyzed. The maximum standardized uptake value (SUVmax) of the positive lesion was measured. The relationship between the SUVmax and C reactive protein (CRP) was analyzed with Pearson correlation. The SUVmax and the number of lesion sites were compared by two-sample t test between the CRP-elevated and CRP-normal patients. Results A total of 56 lesions in the 14 of 15 AAV patients were detected by PET/CT. The positive findings distributed in 15 tissues and organs, including the nasopharynxes (n=9), lungs (n=9), kidneys (n=8), spleen (n=6), lymph nodes (n=6), bone marrow (n=4), skin (n=3), prostate (n=2), aortas (n=2), vertebral soft tissues (n=2), orbita (n=1), parotid gland (n=1), thyroid gland (n=1), liver (n=1) and pancreas (n=1). The 60.7% (34/56) of lesions were clinically unsuspected occult lesions. GPA lesions mainly invaded the nasopharynxes, lungs and kidneys; MPA lesions mainly invaded the kidneys and spleen; EGPA lesions mainly invaded the nasopharynxes, lymph nodes and bone marrow. There was no significant correlation between the level of CRP and the SUVmax of AAV lesions (r=0.462, P>0.05). No differences in the SUVmax were observed between patients with elevated CRP levels and those with normal CRP levels (t=1.451, P>0.05). But more lesion sites were observed in patients with elevated CRP (t=3.456, P<0.05). Conclusions 18F-FDG PET/CT shows positive findings in multiple sites in AAV patients, including clinically unsuspected sites. This imaging technique may be a useful tool for diagnosis and evaluation of AAV. Key words: Anti-neutrophil cytoplasmic antibody-associated vasculitis; Positron-emission tomography; Tomography, X-ray computed; Deoxyglucose