Uptake mechanisms of L-3-[I-125]iodo-alpha-methyl-tyrosine in a human small-cell lung cancer cell line: comparison with L-1-[C-14]tyrosine

The radiolabelled amino acid analogue L-3-[I-125]iodo-alpha-methyl-tyrosine (IMT) is under evaluation in brain tumours, where it reflects amino acid t ransport activity, but is also taken up in many other tumour types. This st udy investigated the uptake mechanism of IMT in tumour cells not derived fr om brain tumours, in comparison with the native amino acid C-14-tyrosine (T yr) from which IMT is derived. Human GLC4 small-cell lung cancer cells in l og-phase were incubated with IMT and Tyr. Tracer uptake was determined in v arious buffers, incubation periods, concentrations of specific amino acid t ransport blockers, pH and temperature. IMT uptake was very fast, reaching a plateau within 5 min, while Tyr kept on accumulating for > 60 min. Based o n steady-state experiments, > 90% of IMT uptake could be attributed to amin o acid transport activity. The L transport system was the most important, b oth fur IMT and Tyr. IMT uptake into GLC4 tumour cells is almost completely the result of amino acid transport activity (especially the L system) and is very similar to Tyr uptake. Therefore, also outside the brain, IMT is a metabolic tracer that may reflect the increased amino acid transport that i s characteristic for malignant tumours. ((C) 2001 Lippincott Williams & Wil kins).