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  • 1
    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.
    Type of Medium: Electronic Resource
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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.
    Type of Medium: Electronic Resource
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