A NEAR-INFRARED FLUORESCENT DEOXYGLUCOSE DERIVATIVE FOR OPTICAL IMAGING OF EXPERIMENTAL ARTHRITIS

The purpose of this study is to investigate whether a near-infrared fluorescence(NIRF)probe,Cy5.5-d-glucosamine(Cy5.5-2DG),can image arthritis in collagen-induced arthritic(CIA)mice.The presence of arthritis was verified by both visual examination and micro-computed tomography(MicroCT)imaging.CIA mice were imaged by a micro-positron emission tomography(MicroPET)scanner one hour after intravenous injection of 2-deoxy-2-[18F]fluoro-d-glucose([18F]FDG).After radioactivity of[18F]FDG decayed away,Cy5.5-2DG was injected into a lateral tail vein of the mice.Arthritic tissue targeting and retention of Cy5.5-2DG in CIA mice were evaluated and quantified by an optical imaging system.Inflammatory tissue in CIA mice was clearly visualized by[18F]FDG-MicroPET scan.NIRF imaging of Cy5.5-2DG in the same mice revealed that the pattern of localization of Cy5.5-2DG in the arthritic tissue was very similar to that of[18F]FDG.Quantification analysis further showed that[18F]FDG uptake in arthritic tissues at one hour post-injection(p.i.)and Cy5.5-2DG uptakes at different time points p.i.were all well correlated(r2 over 0.65).In conclusion,Cy5.5-DG can detect arthritic tissues in living mice.The good correlation between the[18F]FDG uptake and Cy5.5-2DG accumulation in the same arthritic tissue warrants further investigation of Cy5.5-2DG as an approach for assessment of anti-inflammatory treatments.

The role and mechanism of 2deoxyglucose in reversing osimertinibacquired resistance of nonsmall cell lung cancer cell line

Objective To explore the role and mechanism of 2-deoxyglucose ( 2-dg) in reversing osimertinib-acquiredresistance of non-small cell lung cancer ( NSCLC) cellline. Methods The NSCLC line H1975 (purchased fromthe American Type Culture Collection) was conducted byinduction method in vitro to construct the osimertinib-resistanceNSCLC cell line H1975-OR. The osimertinib-resistanceof H1975-OR cell line was examined by 3-(4,5-Dimethylthiazol-2-yl )-2,5-diphenyltetrazolium bromide(MTT) assay,colony-formation assay,Ki67 incorporationassay and the expression of apoptosis-related protein.The glycolysis level was assayed by the lactic acidproduction measured in the culture medium supernatantof H1975 and H1975-OR. The expression of glycolysiskey enzymes (HK2,GLUT1,P-PKM2) and apoptosisrelatedprotein (BIM,Bcl-2) were detected by Westernblot.

Effects of fluctuating glucose concentrations on oxidative metabolism of glucose in cultured neurons and astroglia

The objective of the present study was to evaluate the effects of hyperglycemia on glucose metabolism of brain cells. Not only a sustained hyperglycemic state, but also a fluctuating plasma glucose concentration has been implicated in the pathogenesis of diabetic angiopathy. Acutely increasing plasma glucose levels have not been reported to alter glucose utilization of the brain as a whole. In the present study, we examined the effects of chronic (3 weeks) or short-term (24-hour) exposure to a high glucose concentration on the oxidative metabolism of neurons and astroglia. Cells were prepared from Sprague-Dawley rats and cultured in the presence of a high (22 mM) or low (5 mM) concentration of glucose. The high or low glucose media did not alter either the rates of [14C]deoxyglucose phosphorylation (an indicator of total glucose utilization) or [14C]lactate and [14C]pyruvate oxidation (indicators of oxidative glucose metabolism) in neurons. In contrast, chronic or short-term exposure to a high glucose concentration resulted in significant decreases in oxidation of [14C]acetate, an astrocyte-specific reporter molecule, or [14C]lactate and [14C]pyruvate oxidation in the astroglia. Thus, either chronic or short-term increases in the glucose concentration suppressed oxidative metabolism only in astroglia, indicating neuro-protective roles against hyperglycemic brain cell injury in diabetes mellitus. These different responses of neurons and astroglia may also shed new light on brain energy metabolism in diabetic patients with either chronic high or fluctuating plasma glucose concentrations.

^(18)F-FDG uptake as a biologic factor predicting outcome in patients with resected non-small-cell lung cancer

Background The outcome of surgical treatment of non-small-cell lung cancer （NSCLC） remains poor. In many patients the biological behavior of NSCLC does not follow a definite pattern, and can not be accurately predicted before treatment. ^18F-fluoro-2-deoxy-glucose （^18F-FDG） uptake on positron-emission tomography （PET） is associated with the aggressiveness of NSCLC. The present study focused on the role of ^18F-FDG uptake in predicting the outcome of surgically treated patients with NSCLC. Methods A retrospective analysis was made of 82 patients who underwent complete resection and preoperative FDG PET. The maximum standardized uptake value （SUVmax）, in addition to five clinicopathological factors and three biomolecular factors, which could possibly influence survival, was compared for possible association with patients＇ recurrence and survival, by the Log-rank test in univariate analysis and the Cox proportional hazards model in multivariate analysis. The association between SUVmax and other factors was also analyzed. Results Patients with SUVmax more than 11 had a disease-free survival and overall survival shorter than patients with SUVmax less than 11 in univariate analyses （P〈0.001, P=0.002）. In the multivariate analysis, SUVmax （dichotomized by 11） was the only significant predictor for tumor recurrence. TNM stage and SUVmax （dichotomized by 11） were independent predictors for the overall survival. Associations of SUVmax with p53 overexpression, proliferating cell nuclear antigen （PCNA） labeling index and microvascular density of the tumor were significant in the entire group. Conclusions ^18F-FDG uptake on PET may be used to noninvasively assess biological aggressiveness of NSCLC in vivo, identifying the surgically-treated patients with poor prognosis who could benefit from additional therapy.

Brain glucose metabolism and neuropsychological test in patients with mild cognitive impairment

Objective To investigate the features of regional cerebral metabolic rate of glucose (rCMRglc) in patients with mild cognitive impairment(MCI) by positron emission-tomography and its relationship with neuropsychological test.Methods Positron emission tomography,mini-mental state examination and Wechsler memory scale were applied in 10 patients with MCI and 10 healthy volunteers as the control group. Results Scores of mini-mental state examination and Wechsler memory scale in MCI patients were lower than those in the control group ( P <0.01). rCMRglc of the left orbital gyrus,right middle temporal gyrus and right putamen was lower in the MCI group than in the control group ( P <0.05). Correlation analysis in the MCI group indicated that rCMRglc of many brain regions such as the orbital gyrus,putamen,left hippocampus and parahippocampal gyrus,cingulate gyrus,left amygdaloid body,precentral gyrus,postcentral gyrus,and medial occipitotemporal gyrus in MCI patients,were correlated negatively with age; while the rCMRglc of many parts of the brain such as the left putamen,temporal lobe,anterior cingulate gyrus,left insular lobe,amygdaloid body,precentral gyrus,postcentral gyrus and medial occipitotemporal gyrus were correlated positively with mini-mental state examination; and rCMRglc of the left putamen,temporal lobe,left insular lobe,precentral gyrus and postcentral gyrus were correlated positively with Wechsler memory scale. The right putamen,the right inferior temporal gyrus,precentral gyrus,and left postcentral gyrus were correlated positively with the length of education. However,only rCMRglc of the left amygdaloid body were correlated positively with gender. Conclusion The rCMRglc was lower in the orbital gyrus and putamen of MCI patients. Their rCMRglc were correlated with their cognitive impairment severity,age,length of education and sex.