title: Kinetics of 3-[(123)I]iodo-l-alpha-methyltyrosine transport in rat C6 glioma cells.
abstract: 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.
authors.affiliation: Department of Nuclear Medicine, Westfälische Wilhelms-Universität Münster, Albert-Schweitzer-Strasse 33, D-48129 Münster, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Riemann
authors.forename: F
authors.initials: F
authors.lastname: Stögbauer
authors.forename: K
authors.initials: K
authors.lastname: Kopka
authors.forename: H
authors.initials: H
authors.lastname: Halfter
authors.forename: M
authors.initials: M
authors.lastname: Lasic
authors.forename: A
authors.initials: A
authors.lastname: Schirmacher
authors.forename: T
authors.initials: T
authors.lastname: Kuwert
authors.forename: M
authors.initials: M
authors.lastname: Weckesser
authors.forename: E B
authors.initials: EB
authors.lastname: Ringelstein
authors.forename: O
authors.initials: O
authors.lastname: Schober
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D001932:Brain Neoplasms / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism*; D007202:Indicators and Reagents; D008781:Methyltyrosines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D007202:Indicators and Reagents; D008781:Methyltyrosines; D019275:Radiopharmaceuticals; C030855:3-iodo-alpha-methyltyrosine