Mechanism in cellular uptake of S-11C-methyl-L-cysteine as a tumor imaging agent

Abstract

Objective To investigate the mechanism in uptake of S-11C-methyl-L-cysteine(11C-MCYS) by tumor cells.Methods Hepal-6 cells were divided into Na+ dependent (NaC1 group) and nonNa+ dependent (choline chloride group) groups for amino acids transport experiment.The two groups were then divided into control group,2' - aminobicyclo (2,2,1 ) - heptane-2' - carboxylic acid (BCH,L- amino acid transporter inhibitor),N-methylamino-isobutyric acid (MeAIB,transport system inhibitor of A and ASC) and MeAIB+serine groups.All the groups were added with 11C-MCYS (400 μl 0.925 MBq/ml),11C-MCYS(200μ1 1.85 MBq/ml)+ BCH(200 μ1 15 mmol/L),11C-MCYS(200 μl 1.85 MBq/ml)+ MeAIB(200μl 15 mmol/L),11C-MCYS(200 μ1 1.85 MBq/ml)+ MeAIB+serine(200 μ1 15 mmol/L) respectively.After 4min,the incubation was discontinued,and the cell radioactivity was measured with γ counter.Thereafter,Hepa 1-6 cells were classified into five groups which were added with 200 μl 11C-MCYS( 1.85 MBq/ml)and then different concentrations of MCYS (50,100,200,300,350 μmol/L) for a competitive inhibition experiment.γcounter was used to measure the radioactivity at 4 mins after incubation.Results There were no significant differences in uptake of 11C- MCYS by control,BCH,MeAIB and MeAIB+serine groups with or without the presence of Na + (P＞0.05).In MeAIB and MeAIB + serine groups,the NaC1 and choline chloride sub- groups showed no significant differences in radioactivity (18 958.18±97.32 vs 20 582.27±196.32,18 385.24± 122.96 vs 21 620.54± 131.41,both P＞0.05)and could not inhibit the transportation of non-Na+ dependent amino acid carrier.However in BCH group,the radioactivity in NaC1 group was higher than that in choline chloride group (2587.21 ± 30.25 vs 2340.61 ± 21.09,P＜0.05).Thus,BCH could significantly inhibit the transportation of 11C-MCYS by non-Na+ dependent amino acid carrier.No significant differences were found in uptake of 11C-MCYS by tumor cells under different concentrations of MCYS (50 ～350 μmol/L) (all P＞0.05).Conclusion The uptake of 11C-MCYS is the result of transportation through nonNa+ dependent L-amino acid transport system,with minimal involvement of amino acid transport system A and ASC. Key words: S - 11C - methyl - L - cysteine; Amino acid transport systems,neutral; Positron -emission tomography; Liver neoplasms,experimental; Cell uptake