Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To predict the nature of non-calcifying lung tumors, we performed a prospective study of 46 cases with L-[methyl 11C]methionine (MET, 24 cases) and 18F-fluorodeoxyglucose (FDG, 22 cases) using positron emission tomography (PET). Mean tumor/muscle radioactivity ratios are 5.3 +/- 2.0 (n = 14) for malignant and 1.9 +/- 0.9 (n = 10) for benign with MET (p less than 0.001), and 4.4 +/- 2.2 (n = 12) and 1.5 +/- 0.3 (n = 10), respectively, with FDG (p less than 0.001). The ratios indicate that malignant tumors have higher metabolic demand than benign lesions. Tumors less than 1 cm in diameter were difficult to accurately evaluate due to PET resolution. Compared to the diagnosis at pathology, the MET study showed a sensitivity of 93% (13/14), a specificity of 60% (6/10), and an accuracy of 79% (19/24). The FDG study showed 83% (10/12), 90% (9/10), 86% (19/22), respectively. No significant differences were observed between the two tracers. This study suggests that PET studies using either MET or FDG may be very useful for the differential diagnosis of lung tumors.
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PMID:Differential diagnosis of lung tumor with positron emission tomography: a prospective study. 226 88

We investigated glucose and amino acid metabolism in tumors and other organs using whole body autoradiography with a short-lived positron emitter and a long-lived beta emitter. The radioactive compounds used were 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) with a half life of 109.8 min and L-[methyl-14C]-methionine (14C-MET) with a half life of 5,730 years. A Donryu rat weighing about 150 g was subcutaneously inoculated at the back with experimental tumors of AH109A and AH272. 74 MBq (2 mCi) of 18F-FDG and 740 kBq (20 microCi) of 14C-MET was administered and after 30 min, the rat was sacrificed. Whole body frozen sections were obtained using autocryotome. For the 18F-FDG autoradiogram, the frozen sections were exposed to an X-ray film for 6 h. After seven days, these frozen sections were again exposed to 14C-MET for a week. Cross-contamination was minimized by adjusting the exposure time, the interval of exposures and the administered dose. The accumulation of the tracers was represented as the optical density ratio of the tissue of interest to the muscle. The tumor ratios were 12.5 for 18F-FDG and 8.6 for 14C-MET showing the highest accumulation in the whole body autoradiogram. In contrast the inflammatory tissue ratios were 1.27 for 18F-FDG and 0.77 for 14C-MET showing very low amino acid metabolism. With the present double tracer whole body autoradiogram, 18F-FDG accumulation was seen in the brain and the heart but not to the liver as against 14C-MET accumulation which was seen to the liver but not to the brain and the heart.
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PMID:[Double tracer whole body autoradiography using a short-lived positron emitter and a long-lived beta emitter]. 270 46

Hypoxic accumulation of 2-[5,6-3H]fluoro-2-deoxy-D-glucose ([3H]FDG),L-[methyl-3H] methionine ([3H]MET), and L-[1-3H]leucine ([3H]LEU) was evaluated in two cell lines (UT-SCC-5 and UT-SCC-20) obtained from patients with squamous-cell carcinoma of the head and neck. Both cell lines were exposed to decreasing oxygen atmosphere (20%, 1.5%, or 0% O2) for 6 h, after which they were incubated for a further 1 h with tritiated FDG, MET, or LEU. An anoxic atmosphere resulted in a mean increase of [3H]FDG uptake of 120% and 46% over a baseline 20% oxygen atmosphere for UT-SCC-5 and UT-SCC-20A, respectively. Both total and acid-precipitable [3H]MET uptake remained unchanged at 0% versus baseline, whereas acid-precipitable [3H]LEU uptake decreased by 46% for UT-SCC-5 and by 34% for UT-SCC-20A at 0% O2. Our findings demonstrate that [3H]FDG accumulation is increased in hypoxic UT-SCC cell lines probably through activation of the metabolic steps associated with the glycolytic pathway. The decrease in acid-precipitable [3H]LEU uptake in hypoxia may indicate a decline in protein synthesis, whereas the unchanged [3H]MET uptake probably reflects the unaffected amino acid transport and slow incorporation of radiolabeled methyl group of MET in tumor proteins and nucleic acids. FDG and LEU, but probably not MET, warrant additional study as hypoxia-avid or hypoxia-reduced tracers for assessment of treatment effects designed to modify hypoxia.
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PMID:Influence of hypoxia on tracer accumulation in squamous-cell carcinoma: in vitro evaluation for PET imaging. 900 82

Despite similar benign histological appearances, proliferative activity of meningiomas varies tumor to tumor, and even region to region in a tumor. To predict proliferative potential before surgery, we compared regional uptake of 2-[18F]fluoro-2-deoxyglucose ([18F]FDG) and L-[methyl-11C]methionine ([11C]MET) with histological indices of tumor proliferative activity in 17 specimens from six patients with meningioma obtained by PET guided stereotactic biopsies. Uptake of [11C]MET, an index of protein synthesis rate, significantly correlated not only with the count of nucleolar organizer regions (NORs), a histological index of protein synthesis, but also with Ki-67 index, a histological index of proliferative activity. On the other hand, [18F]FDG uptake showed no significant correlation with Ki-67 index or clinical malignancy. These results suggest that [11C]MET-PET is a useful tool for predicting tumor proliferative potential in meningiomas.
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PMID:Glucose and methionine uptake and proliferative activity in meningiomas. 1055 83

Increasingly hospitals are showing an interest in developing their imaging services to include positron emission tomography (PET). There is therefore a need to be aware of the radiation doses to critical groups. To assess the effective whole-body dose received by technologists within our dedicated PET centre, each staff member was issued with a dose rate meter, and was instructed to record the time spent in contact with any radioactive source, the dose received per working day and the daily injected activity. On average each technologist administered 831 MBq per day. The mean whole-body dose per MBq injected was 0.02 microSv/MBq(-1). The average time of close contact (<2.0 m) with a radioactive source per day was 32 min. The average effective dose per minute close contact was 0.5 microSv/min(-1), which resulted in a mean daily effective dose of 14.4 microSv. No technologist received greater than 60 microSv (the current UK limit for non-classified workers) in any one day, and in general doses received were less than 24 microSv, the daily dose corresponding to the proposed new annual limit for non-classified workers of 6.0 mSv per annum. However, we recognise that the layout of nuclear medicine departments will not mirror our own. We therefore measured the instantaneous dose rates at 0.1, 0.5, 1.0 and 2.0 m from the mid-thorax on 115 patients immediately after injection, to provide estimates of the likely effective doses that might be received by technologists operating dual-headed coincidence detection systems, and others coming into contact in the waiting room with patients who have been injected with fluorine-18 fluorodeoxyglucose. The mean (95th percentile) dose rates measured at the four aforementioned distances were 391.7 (549.5), 127.0 (199.8), 45.3 (70.0) and 17.1 (30.0) microSv/h(-1), respectively. A number of situations have been modelled showing that, with correct planning, FDG studies should not significantly increase the effective doses to technologists. However, one possible area of concern is that, depending on the number of patients in a waiting area at any one time, accompanying persons may approach the limits set by the new UK IRR 1999 regulations for members of the public.
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PMID:Radiation dose rates from patients undergoing PET: implications for technologists and waiting areas. 1085 15

Several studies have shown that the prognosis of oligodendrogliomas is dependent on their histological grade. In order to identify a non-invasive method for the primary diagnosis and follow-up of these tumours, we investigated the relationship between their in vivo metabolism, assessed by positron emission tomography (PET), and their histological grade assessed at the same time. Forty-seven patients with histologically confirmed oligodendrogliomas were investigated. Conventional neuroradiological assessment by computed tomography and magnetic resonance imaging (MRI) was performed in all the patients. All the histology slices were reviewed by the same pathologist after referral from various pathology laboratories. The PET investigation included a carbon-1 methionine (11C-MET) uptake study and, in the majority of cases, a fluorine-18 fluorodeoxyglucose (18F-FDG) uptake study, in order to investigate at the same time both amino acid metabolism and glycolysis. The sampled tumour region of interest (ROI) was defined from the T1-weighted 3D MR scan matched with the PET scan. Tracer concentration in each voxel of the tumour ROI was divided by the mean concentration in an ROI of the same size located in the healthy brain tissue. For each tumour and each tracer, we characterized the metabolic pattern on the basis of the mean and the maximum tumour to healthy tissue concentration ratio, and also the standard deviation and range of the ratios, which indicate the degree of metabolic heterogeneity of the tumour. The histological criteria for differentiating between high- and low-grade tumours were those of the WHO and, partially, of the Sainte-Anne-Daumas-Duport classification. Highly significant differences between high- and low-grade oligodendrogliomas (Mann-Whitney test: P<0.0001) were observed for all the assessed parameters of 11C-MET uptake. On the other hand, the pattern of 18F-FDG uptake showed only moderate differences between the two tumour groups.
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PMID:Non-invasive grading of oligodendrogliomas: correlation between in vivo metabolic pattern and histopathology. 1095 89

The exact incidence of true radiation necrosis is largely unknown. It is probably much less frequent than indicated by MR or CT findings. Differentiating radiation necrosis from recurrent tumor is a diagnostic challenge, however, and has important implications for the patient's management. Even though the first results were published 20 years ago, the total number of case studies using FDG-PET in this indication remains limited. Several reports are also hampered by methodologic limitations. The technique has been largely criticized, notably in articles that themselves were not completely free of methodological flaws. Overall however, FDG-PET seems to be a valuable clinical tool. As a general rule, suspicious lesions on MR imaging that show increased FDG uptake (ie, uptake equal to or great than that in normal cortex) are likely to represent tumor recurrence. Sensitivity is an issue, especially but not exclusively with low-grade gliomas. Although false-positive results may occur, specificity is usually high in routine clinical practice. Coregistration with MR imaging surely improves the diagnostic performances of FDG-PET because it helps delineate the suspicious area. Another important aspect is the prognostic value of FDG uptake, which is now well established. It seems clear that only the combination of FDG with a radiolabeled amino acid analogue (MET or a more recent fluorinated compound) can provide a comprehensive characterization of suspected brain tumor recurrence.
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PMID:PET imaging for differentiating recurrent brain tumor from radiation necrosis. 1569 46

Metabolic imaging with positron emission tomography (PET) provides, in neuro-oncology, information complementary to that provided by anatomic imaging obtained with CT-scanner or MRI. Only a few publications have yet reported its use in oligodendroglial tumors. These findings and partial results obtained in ongoing work, suggest some preliminary conclusions: 11C-MET (L-methyl-methionine) is a more appropriate tracer than 18F-FDG (fluoro-deoxy-glucose), in terms of both specificity and sensitivity, for the assessment of patients with this category of tumor. PET/MET allows differentiation between grade II and grade III oligodendrogliomas; better targeting for stereotactic biopsy; more accurate assessment of the post-operative residual tumor; identification of progression from low-grade to anaplastic grade during the disease course; differentiation between recurrence and a post-radiation processes. PET/MET allows, to some extent, prediction of response to radiotherapy; and, probably, to chemotherapy.
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PMID:[Metabolic imaging for supratentorial oligodendrogliomas]. 1629 75

Biochemical cellular targets and more general metabolic processes in cancer cells can be visualised. Extensive data are available on molecular imaging in preclinical models. However, innovative tracers move slowly to the clinic. This review provides information on the currently available methods of metabolic imaging, especially using PET in humans. The uptake mechanisms of tracer methods and a brief discussion of the more 'molecular' targeted methods are presented. The main focus is on the different classes of tracers and their application in various types of cancer within each class of tracers, based on the current literature and our own experience. Studies with [18F]FDG (energy metabolism), radiolabelled amino acids (protein metabolism), [18F]FLT (DNA metabolism), [11C]choline (cell membrane metabolism) as general metabolic tracer methods and [18F]DOPA (biogenic amine metabolism) as a more specific tracer method are discussed. As an example, molecular imaging methods that target the HER2 receptor and somatostatin receptor are described.
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PMID:Molecular imaging: what can be used today. 1636 Nov 33

Catecholamine-secreting metastatic carcinoid should be considered in differential diagnosis of malignant pheochromocytoma. Paroxysmal functioning or hormonally silent gastroenteropancreatic neuroendocrine tumors (GEP NETs) require repeat biochemical measurements and sensitive anatomic and functional imaging studies overlapping those for malignant pheochromocytoma. This report presents clinical, laboratory, and radiologic findings in a patient presenting with heart rate variability; vasoactive headaches reactive to ethanol, tyramine and tryptophan; labile blood pressure; diaphoresis; diarrhea; abdominal pain; unexplained pancreatitis; joint pain; and paroxysmal flushing with pallor. GI studies (including endoscopic ultrasound) and multiple imaging modalities (including 2D CT, MRI with gadolinium, [18]FDG PET/CT, [123I]MIBG, and SRS [111In]Octreotide [OctreoScan]) were not diagnostic. 24-h BP, Holter and 30-day cardiac event monitors plus urinary biochemical studies consistently suggested catecholamine-synthesizing NET. NIH plasma metanephrines studies and [6]-[18F]Fluorodopamine PET ruled out malignant pheochromocytoma (pheo). Repeated studies showed persistently abnormal GEP NET biomarkers and urinary catecholamines. Capsule endoscopy revealed suspicious submucosal lesions throughout the small intestine. Dual-phase 64-slice multidetector computed tomography (MDCT) with 3D volumetric reconstruction of the abdomen and pelvis revealed multiple diffuse liver metastases and three extrahepatic lesions consistent with metastatic carcinoid. In combination, intensive biochemical testing repeated over time, dual-phase 64-slice MDCT with 3D image reconstruction and volume-rendering (VR) technique, and advanced radionuclide imaging are required to detect NETs' sporadic or paroxysmal functioning, rule out extra-adrenal pheochromocytoma, and localize and characterize metastatic carcinoid. If pheochromocytoma is ruled out, yet symptoms and biochemical markers for catecholamine excess are present, then carcinoid and other amine-precursor-uptake decarboxylation (APUD) tumors must remain in the differential diagnosis.
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PMID:Catecholamine-secreting metastatic carcinoid as differential diagnosis in pheochromocytoma: clinical, laboratory, and imaging clues in the search for the lurking neuroendocrine tumor (NET). 1710 73


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