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

Chemotherapeutic or radiotherapeutic regimens are being increasingly used in low grade glioma of childhood. These protocols require methods to monitor tumor activity. We report our experience in eleven patients. The tumors were localized in the optic pathway (3), cerebral cortex (4) and thalamus/hypothalamus (4). Histological diagnoses included low grade astrocytoma (6), gliofibroma (1) and ganglioglioma (2). Two children with neurofibromatosis type 1 (NF-1) and typical optical tumors were not biopsied. 13 episodes of progression were noted including 3 altered diagnoses. This was evident from clinical symptoms in 11/13 episodes, computed tomography (CT) or magnetic resonance imaging (MRI) in 10/13 situations, iodine-123-alpha-methyltyrosine (123I-IMT) single-photon emission computed tomography (SPECT) in 10/10 situations, fluorine-18 fluorodesoxyglucose (18F-FDG) positron emission tomography (PET) in 0/3 and thallium-201 (201Tl) SPECT in 1/1. Seven responses to chemotherapy were recorded. Clinical symptoms indicated this in 7/7 situations, MRI in 5/7, 123I-IMT SPECT in 1/2 and 201Tl SPECT in 1/1. These data suggest that 123I-IMT SPECT is a valuable addition to low grade glioma diagnostic and stress the need for a prospective study.
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PMID:Monitoring tumor activity in low grade glioma of childhood. 974 59

3-[(123)I]Iodo-l-alpha-methyltyrosine ((123)I-IMT) is used for the diagnosis and monitoring of brain tumours by means of single-photon emission tomography (SPET). To date, little has been known about the system for the transport of (123)I-IMT into brain tumour cells. It is assumed that (123)I-IMT is transported by a specific carrier for large, neutral amino acids (L-system). In this study, rat C6 glioma cells were used to characterize the uptake system of (123)I-IMT and to investigate its precise kinetics. The time course of (123)I-IMT uptake into the cells was examined for a range of 1-60 min. (123)I-IMT uptake rates with varying concentrations of (123)I-IMT (2. 5-50 microM) in the medium were quantified to assess the kinetic parameters of (123)I-IMT transport. Furthermore, competition of (123)I-IMT with other amino acids was investigated to identify the distinct transport systems involved in (123)I-IMT uptake. (123)I-IMT uptake into C6 glioma cells was linear for approximately 10 min and reached a steady-state level within 30 min. The analysis of the rate of uptake of (123)I-IMT at different concentrations was concordant with the predominance of a single uptake system. The apparent Michaelis constant (K(m)) of (123)I-IMT was 26.2+/-1.9 microM, and the maximum transport velocity (V(max)) was 35.4+/-1.7 nmol/mg protein per 10 min. 77%+/-10% of (123)I-IMT transport was sodium independent and 23%+/-3% was sodium dependent. Competitive inhibition of (123)I-IMT uptake by 2-aminobicyclo[2.2. 1]heptane-2-carboxylic acid, alpha-(methylamino)isobutyric acid and naturally occurring amino acids revealed a major (123)I-IMT transport via the sodium-independent system L (72%) and a minor uptake via the sodium-dependent system B(0,+) (17%). Our results show that (123)I-IMT transport into C6 glioma cells is principally mediated by the L-system and to a minor extent by the B(0,+)-system. The kinetic parameters of (123)I-IMT uptake are in the range of those of naturally occurring amino acids.
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PMID:Kinetics of 3-[(123)I]iodo-l-alpha-methyltyrosine transport in rat C6 glioma cells. 1054 25

3-[(123)I]Iodo-L-alpha-methyl tyrosine ((123)I-IMT) is used for diagnosis and monitoring of brain tumours by means of single-photon emission tomography. As recently shown, (123)I-IMT is predominantly mediated into rat C6 glioma cells by sodium-independent system L for large neutral amino acids. Until now, (123)I-IMT transport in non-neoplastic glial cells has not been examined. Therefore, the aim of this study was to examine the cellular pathways and precise transport kinetics of (123)I-IMT uptake into astrocytes of neonatal rats. In particular sodium-independent (123)I-IMT transport into neonatal astrocytes was compared with sodium-independent (123)I-IMT uptake into neoplastic rat C6 glioma cells. Competitive inhibition experiments showed that (123)I-IMT is exclusively transported via sodium-independent system L into the neonatal astrocytes (92%). Kinetic analysis of sodium-independent (123)I-IMT uptake into neonatal astrocytes and into C6 glioma cells revealed apparent Michaelis constants K(M) = 13.9 +/- 0.5 microM and K(M) = 33.9 +/- 4.1 microM, respectively, which are in the same range of K(M) values as those recently determined for amino acid transport into neoplastic and non-neoplastic glial cells. Indeed, the K(M) values in the micromolar range correspond to the expression of the LAT-1 subunit of system L both in the neonatal astrocytes and in C6 glioma cells. However, sodium-independent maximum transport velocities (V(max)) differed significantly between neonatal astrocytes and C6 glioma cells (11.1 +/- 0.3 and 39.9 +/- 3.3 nmol/mg protein/10 min, respectively).
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PMID:Characterization of 3-[(123)I]iodo-L-alpha-methyl tyrosine transport in astrocytes of neonatal rats. 1114 82

3[(123)I]iodo-alpha-methyl-L-tyrosine is a tracer of amino acid transport in brain tumors using single-photon emission-computed tomography and predominantly transported by amino acid transport system L. The 4F2 antigen has been identified to be linked to system L-like transport and is assumed to be a part of the transporter protein. We demonstrated that system L-mediated transport of IMT and 4F2 antigen expression are dependent on proliferation rate of human glioma cells and significantly correlated with each other.
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PMID:3-[123I]iodo-alpha-methyl-L-tyrosine transport and 4F2 antigen expression in human glioma cells. 1118 59

The radiolabelled amino acid 3-[(123)I]iodo-L-alpha-methyl tyrosine ([(123)I]IMT) is a promising tool for the diagnosis and monitoring of brain tumors using single-photon emission tomography (SPECT). However, little is known about the precise kinetics of [(123)I]IMT uptake in human glioma cells. The kinetic analysis of [(123)I]IMT transport in human GOS3 glioma cells yielded a high-affinity apparent Michaelis constant (K(m) = 20.1 +/- 1.5 microM). The maximum transport velocity (V(max)) amounted to 34.8 +/- 1.9 nmol/mg protein/10 min. Competitive inhibition experiments revealed that [(123)I]IMT transport is mediated principally by the sodium-independent system L.
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PMID:Kinetic parameters of 3-[(123)I]iodo-L-alpha-methyl tyrosine ([(123)I]IMT) transport in human GOS3 glioma cells. 1132 40

The aim of this investigation was to compare two current non-invasive modalities, single photon emission tomography (SPECT) using 123-iodine-alpha-methyl tyrosine (123I-IMT) and single-voxel proton magnetic resonance spectroscopy (1H-MRS) at 3.0 T, with regard to their ability to differentiate between residual/ recurrent tumors and treatment-related changes in patients pretreated for glioma. The patient population comprised 25 patients in whom recurrent glioma was suspected based on MR imaging. SPECT imaging started 10 min after iv. injection of 300-370 MBq 123I-IMT and was performed using a triple-head system. The IMT uptake was calculated semiquantitatively using regions-of-interest. 1H-MRS was performed at 3.0 T using the single-volume point-resolved spectroscopy (PRESS) technique. Guided by MR imaging volumes-of-interest for spectroscopy were placed into the suspected lesions. Signal intensities of choline-containing compounds (Cho), creatine and phosphocreatine (Cr), and N-acetylaspartate (NAA) were obtained. When using the cut-off of 1.62 for 123I-IMT uptake, the sensitivity, specificity, and accuracy of the 123I-IMT SPECT were 95, 100 and 96%, respectively. For 1H-MRS, the sensitivity, specificity and accuracy were 89, 83 and 88%, respectively, based both on the metabolic ratios of Cho/Cr and Cho/NAA as tumor criterion with cut-off values of 1.11 and 1.17, respectively. In conclusion, 123I-IMT SPECT yielded more favorable results compared to 1H-MRS at distinguishing recurrent and/or residual glioma from post-therapeutic changes and may be particularly valuable when the evaluation of tumor extent is necessary.
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PMID:123I-IMT SPECT and 1H MR-spectroscopy at 3.0 T in the differential diagnosis of recurrent or residual gliomas: a comparative study. 1552 7

Glioblastoma multiforme still remains, at present, the most frequent and deadly primary malignant glioma in adult. Despite safer and larger neurosurgical resections, patients almost always relapse very close or inside the tumor bed. Since more than 20 years, radiation therapy (RT) continue delivering the same dose of 60 Gy in 6 weeks, more precisely guided with CT-scanner and magnetic resonance imaging (MRI) in the treatment position. If morbidity has decreased with "non whole-brain" volumes, RT is nearly always failing locally, as surgery. Until now, all the series evaluating escalating doses (up to 80-90 Gy) in limited volumes have failed. One can really question : is the good dose delivered in the adequate volume? Main goal of new imaging techniques is to better visualize microscopic extension of malignant glioma cells. As based on metabolic principles, areas of abnormalities visualized with functional imaging have a different meaning, often complementary from conventional data. The four evaluated techniques are : magnetic resonance spectroscoy (MRS), functional MRI (fMRI), 18FDG or methionine PET, IMT (123iodine-alpha-methyl-thyrosine) SPECT. Each technique has potential interests and limits, MRS and fMRI appearing the most promising : they have both acceptable spatial resolution and can be executed just after conventional MRI acquisition. Areas of functional abnormalities are only partially including areas of hyperintensity in T1, T2 weighted MRI. It is therefore highly possible that, using it complementary to conventional CT and MRI for RT treatment planning, they add some precious informations; consequently, the very limited efficacy/toxicity ratio could be increased. This hypothesis will only be confirmed by prospective studies registering in parallel both functional and morphological abnormalities, linking them with sites of local recurrence. Once "targeted" the real microscopically invaded areas, one can speculate on new escalating dose studies, delivering RT in "adequate" volumes, combining it with new "targeted" drugs, as already recently demonstrated in head and neck cancers.
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PMID:[Use of the functional imaging modalities in radiation therapy treatment planning in patients with glioblastoma]. 1588 90