Correlation of Glut-1 glucose transporter expression with [18F]FDG uptake in non-small cell lung cancer

Positron emission tomography (PET) with [¹⁸F]2-fluoro-2-deoxy-D-glucose (FDG) may show negative results for bronchioloalveolar lung carcinoma. We investigated the correlation of Glut-1 glucose transporter expression with [¹⁸F]FDG uptake in non-small cell lung cancer. Thirty-two patients with 34 non-small cell lung cancers (7 bronchioloalveolar carcinomas, 23 non-bronchioloalveolar adenocarcinomas, 3 squamous cell carcinomas, and 1 adenosquamous cell carcinoma) were studied. Final diagnoses were established by histology (via thoracotomy) in all patients. [¹⁸F]FDG PET was performed 40 min after i.v. injection of 185 MBq [¹⁸F]FDG. For semi-quantitative analysis of [¹⁸F]FDG uptake, standardized uptake values (SUVs) were calculated. Glut-1 expression was studied in terms of the immunohistochemistry of paraffin sections using anti-Glut-1 antibody to determine the intensity (0-3) of Glut-1 immunoreactivity and percentage of the Glut-1-positive area. Of seven bronchioloalveolar carcinomas, six (85.7%) were negative for the expression of Glut-1, while only one (4.3%) of 23 non-bronchioloalveolar adenocarcinomas was negative (P<0.0001). The percentages of Glut-1-positive area, as well as the SUVs, were significantly lower in bronchioloalveolar carcinomas (n=7) (2.86%lj.56% and 1.25ǂ.75, respectively) than in non-bronchioloalveolar adenocarcinomas (n=23) (54.83%ᆭ.64%, P<0.0001, and 3.94ǃ.93, P=0.001, respectively). The degree of cell differentiation correlated with the percentage of Glut-1-positive area and SUVs in adenocarcinoma of the lung. Correlations between SUVs and the intensity of Glut-1 immunoreactivity were also significant (intensities 0 and 1, n=11, SUV 1.47ǂ.63; intensities 2 and 3, n=23, SUV 4.78DŽ.13; P<0.0001). The percentage of Glut-1-positive area correlated significantly with SUVs (n=34, r=0.658, P<0.01). Overexpression of Glut-1 correlated with high [¹⁸F]FDG uptake. These findings suggest that Glut-1 expression is related to [¹⁸F]FDG uptake in non-small cell lung cancer. Glut-1 expression, as well as [¹⁸F]FDG uptake, correlated with the degree of cell differentiation in adenocarcinomas, and both Glut-1 expression and [¹⁸F]FDG uptake were significantly lower in bronchioloalveolar carcinomas than in non-bronchioloalveolar carcinomas.     

Glucose uptake and lumped constant variability in normal human hearts determined with [18F]fluorodeoxyglucose

Background  Myocardial glucose uptake can be measured with [¹⁸F]fluoro-2-deoxyglucose (FDG) and positron emission tomography (PET). However, changes of myocardial metabolism may alter the ratio between the net rates of FDG and glucose uptake, known as the lumped constant. We tested the hypothesis that the variability of the lumped constant determined in animals explains the disagreement between human net myocardial glucose uptake calculated from aortocoronary sinus dificits and measured with PET. Methods and Results  In the three-compartment model of glucose transfer into cells, the lumped constant is a function of the relationship between the net and the unidirectional rates of uptake of glucose and glucose tracers such as FDG. Using this principle, validated in the human brain and the animal heart under experimental conditions, we estimated the lumped constant of the human heart by PET in 10 healthy men under several metabolic conditions established by altering the circulating insulin level during a euglycemic clamp and with somatostatin and heparin infusions. The lumped constant varied systematically between 0.44 and 1.35. At insulin levels below 100 pmol/L, free fatty acids were inversely related to serum insulin levels and the lumped constant increased linearly with serum insulin concentration. At insulin levels above 100 pmol/L, free fatty acids were suppressed and the lumped constant varied in inverse proportion to the insulin level. When the lumped constant was estimated in this manner, net myocardial glucose uptake agreed with that determined in previous measurements of blood flow and aortocoronary sinus deficit. Conclusion  In the intact human organism, the cardiac lumped constant varies with the metabolic condition, as predicted from studies of the brain and animal heart under experimental conditions. Supported by grants from the Danish Heart Foundation and the Research Foundation of Aarhus University.     

Subcortical [18F]fluorodeoxyglucose uptake in lesional epilepsy in patients with intracranial tumour

BACKGROUND: We hypothesized that in patients with intracerebral tumours a subcortical metabolical shift may be present when the underlying pathology can, itself, be the epileptogenic focus. We also assumed that by studying the alterations in glucose metabolism beyond the tumour's borders we could identify a modulator area. METHODS: Sixty-seven patients with supratentorial brain tumour associated epilepsy were investigated interictally, in normoglycaemic conditions, by using [18F]fluorodeoxyglucose positron emission tomography (FDG PET). The studies were analysed semiquantitatively by calculating standardized uptake values and asymmetry indices. Normal subjects and patients with non-epileptic brain lesions were used as controls. RESULTS: Compared to normal controls frontal and temporal tumours showed significant changes in thalamic FDG uptake, which reflected hypometabolism of the affected side. It was noted in occipito-medial cortex in temporal tumours and in lentiform nucleus in frontal tumours as well. Comparison to lesional brains only proved that there was significant hypometabolism in lentiform nucleus in temporal tumours. CONCLUSIONS: The quantified values obviously reflect biological changes. The observed subcortical hypometabolism is most likely secondary to underlying pathology. Although seizures in tumorous patients do not originate from subcortical structures their influence on cortical sites of seizure initiation could be explained by defective subcortical regulation of cortical excitability.     

食管癌中18F-氟脱氧葡萄糖摄取和葡萄糖转运蛋白1表达的相关性研究

食管癌的发生和发展涉及多个基因、分子水平的异常,是多个因素参与、共同作用的结果.18F-氟脱氧葡萄糖(18F-FDG)PET检测肿瘤细胞糖摄取在肿瘤诊断、分期、疗效评价、预后判断等方面的应用越来越广泛,而葡萄糖转运蛋白1(Glut-1)在食管癌肿瘤细胞葡萄糖摄取和细胞增殖过程中起重要作用.     

食管癌中18F-氟脱氧葡萄糖摄取和葡萄糖转运蛋白1表达的相关性研究

食管癌的发生和发展涉及多个基因、分子水平的异常,是多个因素参与、共同作用的结果.18F-氟脱氧葡萄糖(18F-FDG)PET检测肿瘤细胞糖摄取在肿瘤诊断、分期、疗效评价、预后判断等方面的应用越来越广泛,而葡萄糖转运蛋白1(Glut-1)在食管癌肿瘤细胞葡萄糖摄取和细胞增殖过程中起重要作用.     

食管癌中18F-氟脱氧葡萄糖摄取和葡萄糖转运蛋白1表达的相关性研究

食管癌的发生和发展涉及多个基因、分子水平的异常,是多个因素参与、共同作用的结果.18F-氟脱氧葡萄糖(18F-FDG)PET检测肿瘤细胞糖摄取在肿瘤诊断、分期、疗效评价、预后判断等方面的应用越来越广泛,而葡萄糖转运蛋白1(Glut-1)在食管癌肿瘤细胞葡萄糖摄取和细胞增殖过程中起重要作用.     

食管癌中18F-氟脱氧葡萄糖摄取和葡萄糖转运蛋白1表达的相关性研究

食管癌的发生和发展涉及多个基因、分子水平的异常,是多个因素参与、共同作用的结果.18F-氟脱氧葡萄糖(18F-FDG)PET检测肿瘤细胞糖摄取在肿瘤诊断、分期、疗效评价、预后判断等方面的应用越来越广泛,而葡萄糖转运蛋白1(Glut-1)在食管癌肿瘤细胞葡萄糖摄取和细胞增殖过程中起重要作用.     

食管癌中18F-氟脱氧葡萄糖摄取和葡萄糖转运蛋白1表达的相关性研究

食管癌的发生和发展涉及多个基因、分子水平的异常,是多个因素参与、共同作用的结果.18F-氟脱氧葡萄糖(18F-FDG)PET检测肿瘤细胞糖摄取在肿瘤诊断、分期、疗效评价、预后判断等方面的应用越来越广泛,而葡萄糖转运蛋白1(Glut-1)在食管癌肿瘤细胞葡萄糖摄取和细胞增殖过程中起重要作用.     

食管癌中18F-氟脱氧葡萄糖摄取和葡萄糖转运蛋白1表达的相关性研究

食管癌的发生和发展涉及多个基因、分子水平的异常,是多个因素参与、共同作用的结果.18F-氟脱氧葡萄糖(18F-FDG)PET检测肿瘤细胞糖摄取在肿瘤诊断、分期、疗效评价、预后判断等方面的应用越来越广泛,而葡萄糖转运蛋白1(Glut-1)在食管癌肿瘤细胞葡萄糖摄取和细胞增殖过程中起重要作用.     

脑肿瘤的组织间近距离放射治疗

组织间近距离放射治疗可提升脑肿瘤局部照射剂量,对于经过选择的原发和复发恶性脑胶质瘤及单发脑转移瘤患者,能提高局部控制率,延长生存期,且无严重的放射并发症,是一种安全、有效的辅助性治疗方法.     

食管癌中18F-氟脱氧葡萄糖摄取和葡萄糖转运蛋白1表达的相关性研究

食管癌的发生和发展涉及多个基因、分子水平的异常,是多个因素参与、共同作用的结果.18F-氟脱氧葡萄糖(18F-FDG)PET检测肿瘤细胞糖摄取在肿瘤诊断、分期、疗效评价、预后判断等方面的应用越来越广泛,而葡萄糖转运蛋白1(Glut-1)在食管癌肿瘤细胞葡萄糖摄取和细胞增殖过程中起重要作用.     

食管癌中18F-氟脱氧葡萄糖摄取和葡萄糖转运蛋白1表达的相关性研究

食管癌的发生和发展涉及多个基因、分子水平的异常,是多个因素参与、共同作用的结果.18F-氟脱氧葡萄糖(18F-FDG)PET检测肿瘤细胞糖摄取在肿瘤诊断、分期、疗效评价、预后判断等方面的应用越来越广泛,而葡萄糖转运蛋白1(Glut-1)在食管癌肿瘤细胞葡萄糖摄取和细胞增殖过程中起重要作用.     

食管癌中^18F-氟脱氧葡萄糖摄取和葡萄糖转运蛋白1表达的相关性研究

食管癌的发生和发展涉及多个基因、分子水平的异常,是多个因素参与、共同作用的结果。^18F-氟脱氧葡萄糖（^18F-FDG）PET检测肿瘤细胞糖摄取在肿瘤诊断、分期、疗效评价、预后判断等方面的应用越来越广泛,而葡萄糖转运蛋白1（Glut-1）在食管癌肿瘤细胞葡萄糖摄取和细胞增殖过程中起重要作用。     

Influence of rhTSH on [18F]fluorodeoxyglucose uptake by differentiated thyroid carcinoma

The influence of serum TSH levels on fluorine-18 fluorodeoxyglucose (FDG) uptake by recurrences or metastases of differentiated thyroid carcinomas has not yet been clarified. The aim of this study was to ascertain whether the administration of recombinant human thyrotropin (rhTSH) stimulates FDG uptake by such lesions. In this prospective study, 30 patients with positive or equivocal thyroglobulin (Tg) levels and negative or equivocal iodine-131 and/or morphological imaging results (ultrasound, MRI, CT) underwent FDG positron emission tomography (PET) under exogenous TSH suppression and under exogenous TSH stimulation of serum levels by injection of rhTSH. The mean interval between the FDG-PET studies under these two conditions was 9.3+/-8.8 weeks. Serum TSH levels and free thyroid hormones were determined on each occasion. FDG uptake was quantitated using tumour to background ratios (TBRs) and standardised uptake values (SUVs). Under TSH suppression there was focal FDG accumulation in nine subjects (22 tumour-like lesions). The total number of foci was 45. After exogenous TSH stimulation, the number of patients in whom FDG foci were detected was 19, and the number of foci identified was 82 (78 tumour-like lesions). TBR of regions showing positive FDG contrast with either of the modalities averaged 2.54+/-1.89, and under stimulated TSH levels, 5.51+/-2.99 ( P<0.0001). Corresponding SUVs were 2.05+/-1.45 versus 2.77+/-1.58 ( P<0.001). In a small number ( n=4) of foci related to inflammatory lymph nodes, TBR and SUV were only marginally increased under TSH stimulation (2.01+/-0.38 and 1.07+/-0.38, respectively), and the values did not differ significantly from those obtained under suppression. These results provide the first direct evidence that TSH stimulates FDG uptake by differentiated thyroid carcinoma and that, therefore, FDG-PET is more accurate under rhTSH than under suppression.     

Effect of steroids on [18F]fluorodeoxyglucose uptake in an experimental tumour model

BACKGROUND: It is well known that blood glucose level affects the uptake of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in tumours. Thus, the action of steroids on glucose metabolism may alter blood glucose levels and may affect FDG uptake in tumours in patients treated with steroids. To clarify this point, we determined the effects of steroids on FDG uptake in tumours in a rat model of a malignant tumour. METHODS: Rats were inoculated with allogenic hepatoma cells (KDH-8) into the left calf muscle. They were fasted overnight and divided into three groups (n=5 in each group): (1) dexamethasone (DEX) pretreated (0.8 mg.kg(-1) body weight, i.m. injection 4 h before FDG i.v. injection); (2) prednisolone (PRE) pretreated (8 mg.kg(-1) body weight, i.m. injection 20 h before FDG i.v. injection); and (3) control (untreated) groups. Radioactivity in tissues was determined 1 h after i.v. injection of FDG. FDG uptake in the tumour was expressed as the percentage of injected dose per gram of tissue after normalization to animal's weight (%ID/g tissue/kg body weight). RESULTS: DEX and PRE pretreatments significantly increased the blood glucose levels to 128% and 145% of the control value. The levels of FDG uptake in the tumour were not significantly affected by DEX and PRE pretreatment (90% and 87% of the control value, respectively) (P=NS). CONCLUSIONS: These results demonstrate that FDG uptake in the tumour was not affected by pretreatment with steroids, in spite of a slight elevation in blood glucose level.     

Thymidine phosphorylase influences [18F]fluorothymidine uptake in cancer cells and patients with non-small cell lung cancer

Purpose

Thymidine phosphorylase (TP), a key enzyme in the pyrimidine nucleoside salvage pathway, catalyses the reversible phosphorylation of thymidine, thereby generating thymine and 2-deoxy-D-ribose-1-phosphate. By regulating the levels of endogenous thymidine, TP may influence [¹⁸F]fluorothymidine ([¹⁸F]FLT) uptake. We investigated the effect of TP activity on [¹⁸F]FLT uptake by tumours.

Methods

Uptake of [³H]FLT and [³H]thymidine ([³H]Thd) and the activities of TP, thymidine kinase 1 (TK1), and equilibrative nucleoside transporter 1 (ENT1) were determined in exponentially growing A431, A549, HT29, HOP92, ACHN, and SKOV3 cells in the presence or absence of tipiracil hydrochloride, a TP inhibitor. Eighty-five non-small cell lung cancer tissues from a patient cohort that was previously studied with [¹⁸F]FLT positron emission tomography (PET) were retrieved and subjected to immunohistochemical analysis of TP expression. Factors that affected the maximum standardised uptake value (SUVmax) of [¹⁸F]FLT-PET were identified by multiple linear regression analysis.

Results

A431 cells had the highest TP activity; A549 and HT29 cells had moderate TP activity; and ACHN, SKOV3, and HOP92 cells had little detectable TP activity. Cell lines with high TP activity took up more [³H]FLT than [³H]Thd, whereas cells with little TP activity took up more [³H]Thd than [³H]FLT. In cells with high TP activity, TP inhibition decreased [³H]FLT uptake and increased [³H]Thd uptake. However, TP inhibition had no effect on ACHN, SKOV3, and HOP92 cells. TP inhibition did not change TK1 or ENT1 activity, but did increase the intracellular level of thymidine. The SUVmax of [¹⁸F]FLT was affected by three independent factors: Ki-67 expression (P?<?0.001), immunohistochemical TP score (P?<?0.001), and tumour size (P?=?0.015).

Conclusions

TP activity influences [¹⁸F]FLT uptake, and may explain preferential uptake of [¹⁸F]FLT over [³H]Thd. These results provide important insights into the biology of [¹⁸F]FLT as a proliferation marker.     

A comparative study of 11C-choline PET and [18F]fluorodeoxyglucose PET in the evaluation of lung cancer

The purpose of this study was to compare the diagnostic value of 11C-choline positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG) PET imaging in the detection of primary lung cancer and mediastinal lymph node metastases. Seventeen patients with histologically proven primary lung cancer were examined with both 11C-choline and FDG PET within a week of each study. Lung cancers were analysed visually and semiquantitatively using the ratio of tumour-to-normal radioactivity (T/N ratio) and standardized uptake value (SUV). Mediastinal lymph node metastases were analysed visually. Although both techniques delineated focal lesions with an increase in tracer accumulation in 13 patients, FDG PET identified three additional patients in whom 11C-choline PET did not visualize any lesion. In the detection of lung cancer <2 cm in size, FDG PET provided higher sensitivity (six of seven, 85.7%) than 11C-choline PET (four of seven, 57.1%). The T/N ratio and SUV were significantly higher with FDG PET (T/N ratio, 7.43+/-6.22; SUV, 4.05+/-3.05) than these were with 11C-choline PET (T/N ratio, 2.93+/-1.19; SUV, 2.93+/-0.79) (P<0.001). There was a significant positive correlation between the T/N ratios and SUVs of FDG and 11C-choline. In the assessment of mediastinal lymph node involvement, FDG PET detected lymph node metastases in two patients who were negative on 11C-choline PET, whereas both techniques could not detect tumour involvement in one patient. Both techniques have clinical value for the non-invasive detection of primary lung cancer that is 2 cm or greater in size. However, FDG PET is superior to 11C-choline PET in the detection of lung cancer that is less than 2 cm in diameter and in mediastinal lymph node metastases.     

Effect of corrections for blood glucose and body size on [18F]FDG PET standardised uptake values in lung cancer

Standardised uptake values (SUVs) are commonly used as a semi-quantitative index of 2-[¹⁸F]fluoro-2-deoxy-D-glucose (FDG) tracer uptake in positron emission tomography (PET). Studies have shown that SUVs may depend on body size and blood glucose concentration and corrections for these effects have been proposed in the literature. This retrospective study investigated the effect of the proposed corrections on SUVs from a group of 154 patients with lung cancer who had scans on a dedicated PET scanner. A total of 252 SUVs were requested as an aid to staging during consideration for surgical resection. SUVs were calculated normalised to body weight (SUV_W), lean body mass (SUV_LBM) and body surface area (SUV_BSA). The following correlations were examined: SUV with height, weight and body surface area for the different body size normalisations; SUV_W and SUV_W 2 blood glucose (SUV_BG) with blood glucose; SUV_W with scan time post injection; and SUV_W with apparent lesion diameter. Significant correlations were only observed between: SUV_LBM and height (P=0.007); SUV_W and scan time (P=0.007); SUV_W and lesion diameter (P=0.0005); and SUV_BG and blood glucose (P<0.00001). The correlation between SUV_LBM and height suggests that lean body mass as a function of height alone should not be used to normalise SUVs; however, the lean body mass calculated from a height and weight nomogram did not show this effect. The strong correlation between SUV_BG and blood glucose concentration suggests that for non-diabetic fasted patients, lung tumour SUVs should not be adjusted for blood glucose.