Kinetics of 3-[I-123]iodo-L-alpha-methyltyrosine transport in rat C6 glioma cells

3-[I-123]Iodo-L-alpha-methyltyrosine (I-123-IMT) is used for the diagnosis and monitoring of brain rumours by means of single-photon emission tomograp hy (SPET). To date, little has been known about the system for the transpor t of I-123-IMT into brain tumour cells. It is assumed that I-123-IMT is tra nsported by a specific carrier for large, neutral amino acids (L-system). I n this study, rat C6 glioma cells were used to characterize the uptake syst em of I-123-IMT and to investigate its precise kinetics. The time course of I-123-IMT uptake into the cells was examined for a range of 1-60 min. I-12 3-IMT uptake rates with varying concentrations of I-123-IMT (2.5-50 mu M) i n the medium were quantified to assess the kinetic parameters of I-123-IMT transport. Furthermore, competition of I-123-IMT with other amino acids was investigated to identify the distinct transport systems involved in I-123- IMT uptake. I-123-IMT uptake into C6 glioma cells was linear for approximat ely 10 min and reached a steady-state level within 30 min. The analysis of the rate of uptake of I-123-IMT at different concentrations was concordant with the predominance of a single uptake system. The apparent Michaelis con stant (K-m) of I-123-IMT was 26.2+/-1.9 mu M, and the maximum transport vel ocity (V-max) was 35.4+/-1.7 nmol/mg protein per 10 min. 77%+/-10% of I-123 -IMT transport was sodium independent and 23%+/-3% was sodium dependent. Co mpetitive inhibition of I-123-IMT uptake by 2-aminobicyclo[2.2.1]heptane-2- carboxylic acid, alpha-(methylamino)isobutyric acid and naturally occurring amino acids revealed a major I-123-IMT transport via the sodium-independen t system L (72%) and a minor uptake via the sodium-dependent system B-0,B- (17%). Our results show that I-123-IMT trans port into C6 glioma cells is principally mediated by the L-system and to a minor extent by the B-0,B-+-s ystem. The kinetic parameters of I-123-IMT uptake are in the range of those of naturally occurring amino acids.