Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Background and Purpose: [F-18]FDG has long been used for detection of the malignant tumors and assessment of the metabolic activity of the tumors. However, there are several drawbacks of FDG including hyperglycemic effect, nonspecific uptake on inflammation, sink phenomenon due to high accumulation of FDG in urinary tract, and physiologic uptake of FDG in the bowels and muscles, which may cause false positive as well as false negative results. [C-11]acetate, as a metabolic substrate of beta-oxidation, precursors of amino acid, fatty acid and sterol, has been proved useful in detecting various malignancies. The aim of this study is to assess the feasibility of clinical application of [C-11]acetate in oncology.Methods: High quality whole body images could be obtained by using large dosage (20 mCi) of [C-11]acetate and modern PET scanner. In the recent years, [C-11]acetate PET studies have been performed in 513 patients with various malignancies.Results: The results showed that [C-11]acetate is more accurate in detecting meningioma (accuracy 97%), glioma (91%), nasopharyngeal cancer (93%), lymphoma (85%), non-small cell cancer (81%), colon cancer (78%), renal cell cancer (80%), ovarian cancer (76%), than in detecting small cell cancer of lung, thyroid cancer, and pancreas cancer. The advantages of [C-11]acetate are less time consuming (whole procedure completed within 45 min after injection), no hyperglycemic effect and no sink phenomenon. The disadvantages are increased uptake in salivary glands, pancreas, and sometimes the bowels, which may cause either false positive or false negative results, and on-site-cyclotron dependent.Conclusion: In summary, [C-11]acetate is clinically useful in detecting various malignant tumors clinically and may play a complementary role to FDG.
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PMID:31. Clinical Application of 1115 Jul 88

The fact that some brain tumors show hypo- or isometabolism on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) has caused problems in the detection of primary or recurrent tumors and in the differentiation from benign lesions. We investigated the usefulness of carbon-11 methionine PET in characterizing brain lesions under these conditions. 11C-methionine PET was performed in 45 patients with brain lesions (in 34 for initial diagnosis and in 11 for detection of recurrence) that showed hypo- or isometabolism compared with normal brain tissue on FDG PET. Ten minutes after the injection of 555-740 MBq of 11C-methionine, attenuation-corrected brain images were obtained with a dedicated PET scanner. The brain lesions comprised 24 gliomas, five metastatic brain tumors, four meningiomas, two other brain tumors and ten benign lesions (including three cases of cysticercosis, two cases of radiation necrosis, one tuberculous granuloma, one hemangioma, one benign cyst, and one organizing infarction). Proliferative activity was measured using the Ki-67 immunostaining method in glioma tissues. Thirty-one of 35 brain tumors (89% sensitivity) showed increased 11C-methionine uptake despite iso- or hypometabolism on FDG PET. By contrast, all ten benign lesions showed decreased or normal 11C-methionine uptake (100% specificity). Twenty-two of 24 gliomas (92%) showed increased 11C-methionine uptake, the extent and degree of which exceeded 18F-FDG uptake, and the 11C-methionine uptake correlated with the proliferation index (r=0.67). The mean (+/-SD) uptake ratios of glioma to normal brain on FDG and 11C-methionine PET were 0.92+/-0.34 and 2.54+/-1.25, respectively. All metastatic tumors except one showed intense 11C-methionine uptake in the entire tumor or in the peripheral margin of the tumor. In meningiomas, 11C-methionine uptake showed a variable increase. In conclusion, brain lesions that show hypo- or isometabolism on FDG PET can be detected and differentiated with high sensitivity and good contrast using 11C-methionine PET. 11C-methionine PET can provide additional information when used in combination with FDG PET in the evaluation of these patients.
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PMID:Usefulness of 11C-methionine PET in the evaluation of brain lesions that are hypo- or isometabolic on 18F-FDG PET. 1192 79

Energy metabolism measurements in gliomas in vivo are now performed widely with positron emission tomography (PET). This capability has developed from a large number of basic and clinical science investigations that have cross fertilized one another. This article presents several areas that exemplify questions that have been explored over the last two decades. While the application of PET with [(18)F]-2-fluoro-2-deoxyglucose (FDG-PET) has proven useful for grading and prognosis assessments, this approach is less clinically suitable for assessing response to therapy, even though results to date raise very intriguing biological questions. Integration of metabolic imaging results into glioma therapy protocols is a recent and only preliminarily tapped method that may prove useful in additional trials that target DNA or membrane biosynthesis, or resistance mechanisms such as hypoxia. There are exciting future directions for molecular imaging that will undoubtedly be fruitful to explore, especially apoptosis, angiogenesis and expression of mutations of genes, e.g., epidermal growth factor receptor, that promote or suppress cellular malignant behavior.
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PMID:Molecular imaging of regional brain tumor biology. 1255 99

To clarify the biological significance of [18F]fluorodeoxyglucose (18F-FDG) accumulation in patients with cancer, we assessed the relationships between 18F-FDG uptake and glucose transporter-1 (GLUT-1) expression and proliferation rate in human glioma and lung cancer. We obtained FDG PET images and measured standardized uptake values (SUVs) of primary tumours in 13 patients with brain glioma and 25 patients with non-small-cell lung cancer. After surgery, portions of respected tumours were obtained, and the proliferation rate was measured as proliferation index (per cent of (S+G2+M)/(G0+G1+S+G2+M)) using DNA flow cytometry. The expression of GLUT-1 in a tumour was evaluated by using immunostaining. We classified GLUT-1 expression as grade 0 (no positive cell), grade 1 (< 10% cells positive), grade 2 (11-50% cells positive) and grade 3 (51-100% cells positive). Based on the expression of GLUT-1, cases with grades 0, 1, 2 and 3 showed SUVs of 6.1 +/- 2.8, 5.0 +/- 3.2, 8.3 +/- 3.3 and 10.4 +/- 6.6, respectively (P < 0.05). Non-small-cell lung cancer showed higher FDG uptake (SUV, 8.5 +/- 5.1) and higher GLUT-1 expression (grade, 2.0 +/- 1.0) than did brain glioma (SUV, 4.7 +/- 2.5; grade, 0.8 +/- 0.8). Based on the total number of cases, SUVs did not relate to proliferation index (r = 0.19). In non-small-cell lung cancer, SUVs did not correlate with proliferation index, whereas in glioma, SUVs were strongly related to proliferation index (r = 0.79, P < 0.01). In conclusion, FDG uptake generally correlated with GLUT-1 expression in non-small-cell lung cancer and glioma. In the case of glioma, FDG uptake also indicated increased cellular proliferation, which was not demonstrated in non-small-cell lung cancer.
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PMID:Comparison of [18F]fluorodeoxyglucose uptake with glucose transporter-1 expression and proliferation rate in human glioma and non-small-cell lung cancer. 1506 Dec 60

One of the biochemical "hallmarks" of malignancy is enhanced tumor glycolysis, which is primary due to the overexpression of glucose transporters (GLUTs) and the increased activity of mitochondria-bound hexokinase in tumors. Easy methods for assessing glucose utilization in vitro and in vivo should find widespread application in biological and biomedical studies, as illustrated by the adoption of FDG PET imaging in medicine. We have recently synthesized a new NIR fluorescent pyropheophorbide conjugate of 2-deoxyglucose (2DG), Pyro-2DG, as a GLUT-targeted photosensitizer. In this study, we have evaluated the in vivo uptake of Pyro-2DG and found that Pyro-2DG selectively accumulated in two tumor models, 9L glioma in the rat and c-MYC-induced mammary tumor in the mouse, compared to surrounding normal muscle tissues at a ratio of about 10:1. By simultaneously performing redox ratio and fluorescence imaging, a high degree of correlation between the PN/(Fp+PN) redox ratio, where PN denotes reduced pyridine nucleotides (NADH) and Fp denotes oxidized flavoproteins, and the Pyro-2DG uptake was found in both murine tumor models, indicating that Pyro-2DG could serve as an extrinsic NIR fluorescent metabolic index for the tumors. The fact that only a low level of correlation was observed between the redox ratio and the uptake of Pyro-acid (the free fluorophore without the 2-deoxyglucose moiety) supports the hypothesis that Pyro-2DG is an index of the mitochondrial status (extent of PN reduction) of a tumor.
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PMID:Metabolic imaging of tumors using intrinsic and extrinsic fluorescent markers. 1549 50

Molecular imaging of a suicide transgene's expression will aid the development of efficient and precise targeting strategies, and imaging for cancer cell viability may assess therapeutic efficacy. We used the PET reporter probe, 9-(4-[18F]fluoro-3-(hydroxymethyl)butyl)guanine ([18F]FHBG) to monitor the expression of a mutant Herpes Simplex Virus 1 thymidine kinase (HSV1-sr39tk) in C6 glioma tumors implanted subcutaneously in nude mice that were repetitively being treated with the pro-drug Ganciclovir (GCV). [18F]-Fluorodeoxyglucose ([18F]FDG), a metabolic tracer, was used to assess tumor cell viability and therapeutic efficacy. C6 glioma tumors stably expressing the HSV1-sr39tk gene (C6sr39) accumulated [18F]FHBG prior to GCV treatment. Significant declines in C6sr39 tumor volumes and [18F]FHBG and [18F]FDG accumulation were observed following 2 weeks of GCV treatment. However, 3 weeks after halting GCV treatment, the tumors re-grew and [18F]FDG accumulation increased significantly; in contrast, tumor [18F]FHBG concentrations remained at background levels. Therefore, [18F]FHBG can be used to detect tumors expressing HSV1-sr39tk, susceptible to regression in response to GCV exposure, and the effectiveness of GCV therapy in eradicating HSV1-sr39tk-expressing cells can be monitored by [18F]FHBG scanning. [18F]FHBG and [18F]FDG imaging data indicate that exposure of C6sr39 tumors to GCV causes the elimination of [18F]FHBG-accumulating C6sr39 cells and selects for re-growth of tumors unable to accumulate [18F]FHBG.
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PMID:Imaging progress of herpes simplex virus type 1 thymidine kinase suicide gene therapy in living subjects with positron emission tomography. 1559 47

The aim of this study was to assess simplified methods for deriving input functions for estimating glucose metabolism using 18F-FDG-PET. Nine glioma patients underwent paired 18F-FDG-PET scans as part of a phase II study and the data used to estimate the metabolic rate of glucose (MRGlu) using a population-derived input function (arterial data from 14 scans) scaled using a single arterial blood sample taken at 20 min. Paired studies were performed in four further glioma patients with stable disease at least four months following radiotherapy to determine whether scaling the population-derived input function using a 20-min arterialised venous or venous sample further simplified the method. The heated hand method was used to obtain arterialised venous blood that approximated arterial blood. In the 9 phase II glioma patients, there was a good, statistically significant correlation between the MRGlu values estimated using the individual arterial input functions and the single arterial sample scaled population-derived input functions (r(2)=0.88, p<0.001, n=36). Blood samples collected during three scans on two of the stable disease patients showed no significant difference between the arterialised venous and arterial plasma concentrations of 18F (p>0.1, n=15) when the degree of arterialisation of the blood was monitored and maintained using a thermocouple. A significant difference was found between the plasma arterial and venous levels of 18F. There was an excellent correlation between MRGlu estimated using an arterial input function and a population-derived input function scaled using a single arterialised venous blood sample (r(2)=0.98, n=12). The method was reproducible with less than 4.4% variation between repeat tumour scans. Therefore, a population-derived input function scaled using a single arterialised venous blood sample at 20 min can be used for estimating MRGlu using 18F-FDG PET in glioma patients.
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PMID:Glucose metabolism in brain tumours can be estimated using [18F]2-fluorodeoxyglucose positron emission tomography and a population-derived input function scaled using a single arterialised venous blood sample. 1580 31

The treatment of the glioma patient depends on the nature of the lesion and on the aggressiveness of the tumor. The management of gliomas continues to be a challenging task, because morphological neuroimaging techniques do not always differentiate them from nontumoral lesions or high grade tumors from low grade lesions. Positron Emission Tomography (PET) offers the possibility of the in vivo quantitative characterization of brain tumors. Despite decades of useful application of PET in the clinical monitoring of gliomas, no consensus has been reached on the most effective image analysis approach for providing the best diagnostic performance under heavy-duty clinical diagnostic circumstances. The main objective of the present study was to find and validate optimal semi-quantitative search strategies for metabolic PET studies on gliomas, with special regard to the optimization of those metabolic tracer uptake ratios most sensitive in predicting histologic grade and prognosis. 11C-Methionine (11C-Met, n = 50) and/or 18F-Fluorodeoxyglucose (18F-FDG, n = 33) PET measurements were performed in 59 patients with primary and recurrent brain gliomas (22 high grade and 37 low grade tumors) in order to correlate the biological behavior and 11C-Met/18F-FDG uptake of tumors. Data were analyzed by region-of-interests (ROI) methods using standard uptake value calculation. Different ROI defining strategies were then compared with each other for two of the most commonly used metabolic radiotracers, 18F-FDG and 11C-Met, in order to determine their usefulness in grading gliomas. The results were compared to histological data in all patients. Both ANOVA and receiver operating characteristic (ROC) analysis indicated that the performance of 18F-FDG was superior to that of 11C-Met for most of the ratios. 18F-FDG is therefore suggested as the tracer of choice for noninvasive semi-quantitative indicator of histologic grade of gliomas. 11C-Methionine has been suggested as a complimentary tracer, useful in delineating the extent of the tumor. The best diagnostic performance was obtained by calculating the ratio of the peak 18F-FDG uptake of the tumor to that of white matter (p < 0.001; ANOVA). This metabolic tracer uptake ratio is therefore suggested as an easily obtained semi-quantitative PET indicator of malignancy and histological grade in gliomas.
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PMID:Optimization of semi-quantification in metabolic PET studies with 18F-fluorodeoxyglucose and 11C-methionine in the determination of malignancy of gliomas. 1793 35

2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) has extensively been used for clinical diagnosis, staging, and therapy monitoring of cancer and other diseases. Nonradioactive glucose analogues enabling the screening of the glucose metabolic rate of tumors are of particular interest for anticancer drug development. A nonradioactive fluorescent deoxyglucose analogue may have many applications for both imaging of tumors and monitoring therapeutic efficacy of drugs in living animals and may eventually translate to clinical applications. We found that a fluorescent 2-deoxyglucose analogue, 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG), can be delivered in several tumor cells via the glucose transporters (GLUTs). We therefore conjugated D-glucosamine with a near-infrared (NIR) fluorphor Cy5.5 and tested the feasibility of the Cy5.5-D-glucosamine (Cy5.5-2DG) conjugate for NIR fluorescence imaging of tumors in a preclinical xenograft animal model. Cy5.5-2DG was prepared by conjugating Cy5.5 monofunctional N-hydroxysuccinimide ester (Cy5.5-NHS) and D-glucosamine followed by high-performance liquid chromatography purification. The accumulation of Cy5.5-2DG and Cy5.5-NHS in different tumor cell lines at 37 and 4 degrees C were imaged using a fluorescence microscope. Tumor targeting and retention of Cy5.5-2DG and Cy5.5-NHS in a subcutaneous U87MG glioma and A375M melanoma tumor model were evaluated and quantified by a Xenogen IVIS 200 optical cooled charged-coupled device system. Fluorescence microscopy imaging shows that Cy5.5-2DG and Cy5.5-NHS are taken up and trapped by a variety of tumor cell lines at 37 degrees C incubation, while they exhibit marginal uptake at 4 degrees C. The tumor cell uptake of Cy5.5-2DG cannot be blocked by the 50 mM D-glucose, suggesting that Cy5.5-2DG may not be delivered in tumor cells by GLUTs. U87MG and A375M tumor localization was clearly visualized in living mice with both NIR fluorescent probes. Tumor/muscle contrast was clearly visible as early as 30 min postinjection (pi), and the highest U87MG tumor/muscle ratios of 2.81 +/- 0.10 and 3.34 +/- 0.23 were achieved 24 h pi for Cy5.5-2DG and Cy5.5-NHS, respectively. While as a comparison, the micropositron emission tomography imaging study shows that [18F]FDG preferentially localizes to the U87MG tumor, with resulting tumor/muscle ratios ranging from 3.89 to 4.08 after 30 min to 2 h postadministration of the probe. In conclusion, the NIR fluorescent glucose analogues, Cy5.5-2DG and Cy5.5-NHS, both demonstrate tumor-targeting abilities in cell culture and living mice. More studies are warranted to further explore their application for optical tumor imaging. To develop NIR glucose analogues with the ability to target GLUTs/hexokinase, it is highly important to select NIR dyes with a reasonable molecular size.
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PMID:Near-infrared fluorescent deoxyglucose analogue for tumor optical imaging in cell culture and living mice. 1670 3

A 51-year-old male presented with a 5-year history of progressive right exophthalmos and visual loss. Magnetic resonance imaging showed a right intraorbital lesion. [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) revealed high uptake in the tumor. No FDG was accumulated in the remaining optic tract. He underwent removal of the tumor. The histological diagnosis was optic glioma. Six months after the operation, the tumor recurred, and a second operation was performed to spare the visual acuity of the other eye, which remained stable for 1.5 years after the first operation. However, the patient died 2 years after the first operation of liver dysfunction. Adult optic glioma tends to rapidly extend into the surrounding tissue and to affect the contralateral visual pathway. Early diagnosis and surgical intervention are imperative. In the present case, [(18)F]FDG-PET was valuable for evaluating malignancy to determine whether radical surgery was indicated to preserve the remaining visual acuity.
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PMID:Surgical decision for adult optic glioma based on [18F]fluorodeoxyglucose positron emission tomography study. 1706 90


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