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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 3-[123I]Iodo-L-α-methyl tyrosine (123I-IMT) is used for diagnosis and monitoring of brain tumours by means of single-photon emission tomography. As recently shown, 123I-IMT is predominantly mediated into rat C6 glioma cells by sodium-independent system L for large neutral amino acids. Until now, 123I-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 123I-IMT uptake into astrocytes of neonatal rats. In particular sodium-independent 123I-IMT transport into neonatal astrocytes was compared with sodium-independent 123I-IMT uptake into neoplastic rat C6 glioma cells.Competitive inhibition experiments showed that 123I-IMT is exclusively transported via sodium-independent system L into the neonatal astrocytes (92%). Kinetic analysis of sodium-independent 123I-IMT uptake into neonatal astrocytes and into C6 glioma cells revealed apparent Michaelis constants KM = 13.9 ± 0.5 µm and KM = 33.9 ± 4.1 µm, respectively, which are in the same range of KM values as those recently determined for amino acid transport into neoplastic and non-neoplastic glial cells. Indeed, the KM 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 (Vmax) 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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  • 2
    ISSN: 1439-099X
    Keywords: Key Words: Glioma ; Scintigraphy ; Amino Acid ; SPECT ; Blood brain barrier ; Schlüsselwörter: Gliom ; Szintigraphie ; Aminosäure ; SPECT ; Blut-Hirn-Schranke
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Hintergrund: Die szintigraphische Darstellung der Verteilung des 201Thallium (201T1-SPECT) und der Aminosäure 123I-α-Methyltyrosin (123-I-IMT-SPECT) wird zur Evaluierung von Gliomen eingesetzt. Während die 201T1-Aufnahme analog zum zerebralen Kaliumeinstrom erfolgt, wird 123I-IMT mit Hilfe eines Aminosäurecarriers über die Blut-Hirn-Schranke transportiert. Ziel der Studie war ein Vergleich der Darstellng der Gliomausdehnung mit den beiden Verfahren. Patienten und Methode: 17 Patienten mit malignen Gliomen wurden mit beiden Verfahren untersucht (Astrozytom III: n = 6, Ependymom III: n = 1, Oligodendrogliom III: n = 1, Glioblastom IV: n = 9). Die Schnittbilder wurden anatomisch abgeglichen und die Schicht mit der jeweils maximalen Tumorausdehnung aufgesucht. Die Tumorfläche wurde gemessen und die Tumorausdehnung visuell beurteilt. Ergebnisse: Die Tumorausdehnung stellt sich bei den WHO-III-Tumoren mit 123-I-IMT-SPECT signifikant größer dar als in der 201T1-SPECT (Mittelwert ± Standardabweichung 816 ± 281 Pixels vs. 600 ± 220 Pixels, n = 8, p 〈 0,05, Abbildung 1a), die Größe der Glioblastome war in beiden Untersuchungen vergleichbar (977 ± 571 vs. 1051 ± 588, n = 9, p = 0,57, Abbildung 1b), wobei die visuelle Beurteilung in einigen Fällen regionale Unterschiede der Speicherintensität zeigte. In der Gesamtgruppe ergab sich eine schwache, aber signifikante negative Korrelation zwischen der maximalen 201-T1-Aufnahme einerseits und einem Quotienten aus der mit 123-I-IMT und der mit 201T1 dargestellten Fläche andererseits (n = 17, r = 0,49, p 〈 0,05, Abbildung 2). Somit wurde der Unterschied in der Flächendarstellung mit steigender 201T1-Aufnahme kleiner. Schlussfolgerungen: 123I-IMT-SPECT zeigt bei Gliomen WHO-Grad III eine größere Tumorausdehnung als 201T1-SPECT. Da in früheren Untersuchungen gezeigt wurde, dass in den meisten Fällen eine Störung der Blut-Hirn-Schranke Voraussetzung für die zerebrale 201T1-Akkumulation ist, kann die 123I-IMT-SPECT möglicherweise Tumoranteile darstellen, die keine vermehrte endotheliale Durchlässigkeit aufweisen. Inwiefern diese Zusatzinformation zur Planung einer Operation oder einer Strahlentherapie eingesetzt werden kann, muss in zukünftigen Studien gezeigt werden. Mit steigender Malignität und zunehmender 201T1-Aufnahme nehmen die genannten Vorteile des 123I-IMT ab.
    Notes: Background: Single photon emission computed tomography (SPECT) with 201T1 and 123I-α-methyl tyrosine (123I-IMT) are routine methods for the evaluation of brain tumors. 123-I-IMT transport across the blood brain barrier is mediated by an amino acid carrier, 201T1 accumulation is analogous to cerebral potassium uptake. Patients and Methods: To determine the differences in glioma extension as shown by the 2 methods, 17 patients with malignant gliomas were included in this comparative imaging study: astrocytoma III: n = 6, ependymoma III: n = 1, oligodendroglioma III: n = 1, glioblastoma IV: n = 9. The tomographic image sets were matched anatomically and the slices showing maximal tumor extension were identified in both image sets respectively. Tumor spread was compared visually and the tumor extension was quantified. Results: In gliomas WHO III tumor extension was delineated significantly larger by 123I-IMT-SPECT than by 201T1-SPECT (mean ± SD: 816 ± 281 pixels vs 600 ± 220 pixels, n = 8, p 〈 0.05). The size of glioblastomas was shown in a comparable manner by the 2 methods (977 ± 571 vs 1,051 ± 588, n = 9, ns, p = 0.57), but there were considerable regional differences between the area of 201T1 uptake and amino acid retention. In the whole group a weak but significant negative correlation between intensity of 201T1 uptake on the one hand and a ratio of the area as depicted by 123I-IMT vs area as depicted by 201T1 on the other hand, was found (n = 17, r = 0.49, p 〈 0.05). Thus the differences in the delineation of areas became smaller with increasing 201T1 uptake. Conclusions: These preliminary data indicate that the extension of gliomas is depicted differently by the 2 methods. 123I-IMT-SPECT shows a larger tumor extension especially in gliomas WHO III. Since 201T1 uptake has previously been shown to correlate with disruption of the blood brain barrier, 123I-IMT-SPECT may delineate tumor parts without endothelial leakage. This additional information may be helpful in planning surgical or radiation therapy. The advantages of 123I-IMT in this respect decrease with increasing 201T1 uptake and with increasing malignancy.
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  • 3
    ISSN: 1619-7089
    Keywords: Key words: Cholinergic system ; Muscarinic receptors ; Epilepsy ; Emission tomography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Animal experiments and preliminary results in humans have indicated alterations of hippocampal muscarinic acetylcholine receptors (mAChR) in temporal lobe epilepsy. Patients with temporal lobe epilepsy often present with a reduction in hippocampal volume. The aim of this study was to investigate the influence of hippocampal atrophy on the quantification of mAChR with single photon emission tomography (SPET) in patients with temporal lobe epilepsy. Cerebral uptake of the muscarinic cholinergic antagonist [123I]4-iododexetimide (IDex) was investigated by SPET in patients suffering from temporal lobe epilepsy of unilateral (n=6) or predominantly unilateral (n=1) onset. Regions of interest were drawn on co-registered magnetic resonance images. Hippocampal volume was determined in these regions and was used to correct the SPET results for partial volume effects. A ratio of hippocampal IDex binding on the affected side to that on the unaffected side was used to detect changes in muscarinic cholinergic receptor density. Before partial volume correction a decrease in hippocampal IDex binding on the focus side was found in each patient. After partial volume no convincing differences remained. Our results indicate that the reduction in hippocampal IDex binding in patients with epilepsy is due to a decrease in hippocampal volume rather than to a decrease in receptor concentration.
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  • 4
    ISSN: 1619-7089
    Keywords: Cholinergic system ; Muscarinic receptors ; Epilepsy ; Emission tomography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Animal experiments and preliminary results in humans have indicated alterations of hippocampal muscarinic acetylcholine receptors (mAChR) in temporal lobe epilepsy. Patients with temporal lobe epilepsy often present with a reduction in hippocampal volume. The aim of this study was to investigate the influence of hippocampal atrophy on the quantification of mAChR with single photon emission tomography (SPET) in patients with temporal lobe epilepsy. Cerebral uptake of the muscarinic cholinergic antagonist [123I]4-iododexetimide (IDex) was investigated by SPET in patients suffering from temporal lobe epilepsy of unilateral (n=6) or predominantly unilateral (n=1) onset. Regions of interest were drawn on co-registered magnetic resonance images. Hippocampal volume was determined in these regions and was used to correct the SPET results for partial volume effects. A ratio of hippocampal IDex binding on the affected side to that on the unaffected side was used to detect changes in muscarinic cholinergic receptor density. Before partial volume correction a decrease in hippocampal IDex binding on the focus side was found in each patient. After partial volume no convincing differences remained. Our results indicate that the reduction in hippocampal IDex binding in patients with epilepsy is due to a decrease in hippocampal volume rather than to a decrease in receptor concentration.
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  • 5
    ISSN: 1619-7089
    Keywords: Key words: Rat C6 glioma cells ; l-[123I]Iodo-α-methyltyrosine ; L-system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. 3-[123I]Iodo-l-α-methyltyrosine (123I-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 123I-IMT into brain tumour cells. It is assumed that 123I-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 123I-IMT and to investigate its precise kinetics. The time course of 123I-IMT uptake into the cells was examined for a range of 1–60 min. 123I-IMT uptake rates with varying concentrations of 123I-IMT (2.5–50 µM) in the medium were quantified to assess the kinetic parameters of 123I-IMT transport. Furthermore, competition of 123I-IMT with other amino acids was investigated to identify the distinct transport systems involved in 123I-IMT uptake. 123I-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 123I-IMT at different concentrations was concordant with the predominance of a single uptake system. The apparent Michaelis constant (K m) of 123I-IMT was 26.2±1.9 µM, and the maximum transport velocity (V max) was 35.4±1.7 nmol/mg protein per 10 min. 77%±10% of 123I-IMT transport was sodium independent and 23%±3% was sodium dependent. Competitive inhibition of 123I-IMT uptake by 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid, α-(methylamino)isobutyric acid and naturally occurring amino acids revealed a major 123I-IMT transport via the sodium-independent system L (72%) and a minor uptake via the sodium-dependent system B0,+ (17%). Our results show that 123I-IMT transport into C6 glioma cells is principally mediated by the L-system and to a minor extent by the B0,+-system. The kinetic parameters of 123I-IMT uptake are in the range of those of naturally occurring amino acids.
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  • 6
    ISSN: 1619-7089
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1619-7089
    Keywords: Key words: Brain tumour – Single-photon emission tomography – Iodine-123 α-methyltyrosine – Thallium-201
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Both thallium-201 and iodine-123 α-methyltyrosine (123I-IMT) have been shown to be useful in the diagnostic evaluation of brain tumours. The aim of this study was to investigate the respective contributions of 201Tl and 123I-IMT single-photon emission tomography (SPET) in the non-invasive evaluation of intracerebral tumours. We analysed 65 patients with the following brain tumours: 8 non-neoplastic lesions, 4 meningiomas, 12 low-grade gliomas, 28 high-grade gliomas, 11 metastases and 2 high-grade lymphomas. 201Tl SPET and 123I-IMT SPET were performed [start of 201Tl SPET: 15 min p.i. (early) and 180 min p.i. (delayed); start of 123I-IMT SPET: 15 min p.i.]. The intensity of uptake was quantified as the ratio between tracer accumulation in the tumour and in the contralateral hemisphere. None of the non-neoplastic lesions or low-grade gliomas expressed marked 201Tl uptake. All malignant tumours except one small metastasis and all meningiomas except one small, cystic and degenerated lesion showed significant 201Tl accumulation [Tl(15’)〉2.0]; 123I-IMT uptake was either absent or intermediate in non-malignant lesions except in two low-grade gliomas; the highest levels were observed in high-grade gliomas followed by metastases and lymphomas (mean IMT: 2.7 vs 2.1 vs 1.8), with metastases showing a high variability in 123I-IMT uptake (range: 0.8–3.6). Using 201Tl to distinguish non-neoplastic lesions from malignant tumours and meningiomas, 63 of 65 patients were characterised correctly. In the latter group, high-grade gliomas were correctly identified in 27 of 28 cases by their amino acid uptake. It is concluded that the combination of 201Tl and 123I-IMT surpasses the accuracy of each single test in the differentiation of space-occupying lesions of the brain. Based on these preliminary results, a sequential strategy is proposed involving an initial 201Tl SPET study and an additional 123I-IMT SPET study in the event of positive 201Tl uptake.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1619-7089
    Keywords: Key words: Single-photon emission tomography ; Glioma ; l-3-[123I]iodo-α-methyltyrosine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Single-photon emission tomography (SPET) with the amino acid analogue l-3-[123I]iodo-α-methyl tyrosine (IMT) is helpful in the diagnosis and monitoring of cerebral gliomas. Radiolabelled amino acids seem to reflect tumour infiltration more specifically than conventional methods like magnetic resonance imaging and computed tomography. Automatic tumour delineation based on maximal tumour uptake may cause an overestimation of mean tumour uptake and an underestimation of tumour extension in tumours with circumscribed peaks. The aim of this study was to develop a program for tumour delineation and calculation of mean tumour uptake which takes into account the mean background activity and is thus optimised to the problem of tumour definition in IMT SPET. Using the frequency distribution of pixel intensities of the tomograms a program was developed which automatically detects a reference brain region and draws an isocontour region around the tumour taking into account mean brain radioactivity. Tumour area and tumour/brain ratios were calculated. A three-compartment phantom was simulated to test the program. The program was applied to IMT SPET studies of 20 patients with cerebral gliomas and was compared to the results of manual analysis by three different investigators. Activity ratios and chamber extension of the phantom were correctly calculated by the automatic analysis. A method based on image maxima alone failed to determine chamber extension correctly. Manual region of interest analysis in patient studies resulted in a mean inter-observer standard deviation of 8.7%±6.1% (range 2.7%–25.0%). The mean value of the results of the manual analysis showed a significant correlation to the results of the automatic analysis (r = 0.91, P〈0.0001 for the uptake ratio; r = 0.87, P〈0.0001 for the tumour area). We conclude that the algorithm proposed simplifies the calculation of uptake ratios and may be used for observer-independent evaluation of IMT SPET studies. Three-dimensional tumour recognition and transfer to co-registered morphological images based on this program may be useful for the planning of surgical and radiation treatment.
    Type of Medium: Electronic Resource
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