monoiodotyrosine and Multiple-Myeloma

The aim of this study was to investigate the cellular uptake mechanisms responsible for the accumulation of 3-[(125)I]iodo-L-alpha-methyltyrosine ((125)I-3-IMT) and 2-[(125)I]iodo-L-tyrosine ((125)I-2-IT), two radiotracers for metabolic tumor imaging, using single-photon emission tomography, into U266 human myeloma cancer cells. Time course and concentration dependency of (125)I-3-IMT uptake was assessed. Kinetic parameters were calculated using an Eadie Hofstee plot. A set of competitive inhibitors of the main amino acid transport systems was used for the discrimination of the transporters responsible for the uptake of (125)I-3-IMT and (125)I-2-IT. Protein incorporation of both tracers was determined using acid precipitation. The measured maximum velocity for (125)I-3-IMT transport was 4.199 nmol per mg protein 20 s(-1), and the Michaelis constant was 107.9 microM. Addition of 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH), a competitive inhibitor of System L, reduced the influx by 39.0+/-3.3% for (125)I-3-IMT and 66.3+/-0.9% for (125)I-2-IT. The BCH-insensitive influx was further reduced by Tryptophan (Trp) by 43.8+/-3.5% for (125)I-3-IMT and 15.3+/-1.3% for (125)I-2-IT. This suggests involvement of System T transport. We measured <2% of radioactivity in the acid precipitable fractions of both tracers with no increase in time. We conclude that the influx of (125)I-3-IMT and (125)I-2-IT into U266 human myeloma cells is mediated by both System L and System T amino acid transporters. The kinetic parameters suggest that elevated plasma levels of aromatic amino acids will reduce (123)I-3-IMT uptake in myeloma patients. Both tracers do not enter protein synthesis significantly.

Topics: Amino Acids; Animals; Binding, Competitive; Biological Transport; Female; Gamma Cameras; Humans; Iodine Radioisotopes; Kinetics; Male; Methyltyrosines; Monoiodotyrosine; Multiple Myeloma; Radionuclide Imaging; Rats; Rats, Wistar; Tissue Distribution; Tryptophan; Tumor Cells, Cultured

Topics: Animals; Antibodies, Neoplasm; Antibody Specificity; Antigen-Antibody Reactions; Antigens, Neoplasm; Cell Line; Cytotoxicity Tests, Immunologic; Immune Sera; Immunoglobulin Fab Fragments; Immunoglobulins; Iodine Radioisotopes; Leucine; Lymphoma; Mice; Monoiodotyrosine; Multiple Myeloma; Myeloma Proteins; Papain; Precipitin Tests; Pronase; Rabbits; Sheep; Temperature; Tritium