Transport mechanisms of 3-[123I]iodo-alpha-methyl-L-tyrosine in a human glioma cell line: comparison with [3H]methyl]-L-methionine.
The amino acid analog 3-[(123)I]iodo-alpha-methyl-L-tyrosine (IMT) is under clinical evaluation as a SPECT tracer of amino acid transport in brain tumors. This study investigated the carrier systems involved in IMT transport in human glioma cells in comparison with [3H-methyl]-L-methionine (3H-MET).


METHODS
Human glioma cells, type 86HG-39, were cultured and incubated for 1 min at 37 degrees C with IMT and 3H-MET in the lag phase (1.2 d after seeding), exponential growth phase (3 d after seeding), and plateau phase (8 d after seeding). Experiments were performed in the presence and absence of Na+, during inhibition of system L amino acid transport by 2-aminobicyclo[2.2.1 ]heptane-2-carboxylic acid (BCH), and during inhibition of system A amino acid transport by 2-(methylamino)-isobutyric acid (MeAIB).


RESULTS
IMT and 3H-MET uptake decreased by 55%-73% when the cells entered from the exponential growth phase into the plateau phase (P< 0.05; n = 3-11). Inhibition by BCH reduced uptake of IMT in the lag phase, exponential growth phase, and plateau phase by 90%-98% (P < 0.001; n = 3-6) and the uptake of 3H-MET by 73%-83% (P < 0.001; n = 3-11). In a Na+-free medium 3H-MET uptake was reduced by 23%-33% (P < 0.05; n = 3-11), whereas IMT uptake was not significantly different. MeAIB showed no significant effect on IMT or 3H-MET uptake in either phase.


CONCLUSIONS
Transport of both IMT and 3H-MET depends on the proliferation rate of human glioma cells in vitro and is dominated by BCH-sensitive transport. These data indicate that system L is induced in rapidly proliferating glioma cells and is the main contributor to the uptake of both tracers. 3H-MET transport showed a minor Na+ dependency that was not attributable to system A. The similarity of transport mechanisms of both tracers emphasizes the clinical equivalence of IMT SPECT and (11)C-MET PET for the diagnostic evaluation of gliomas.
Langen
K J
KJ
Institute of Medicine, Research Center Jülich, Germany.
Mühlensiepen
H
H
Holschbach
M
M
Hautzel
H
H
Jansen
P
P
Coenen
H H
HH
D000596:Amino Acids / Q000494:pharmacology; D000598:Amino Acids, Cyclic; D000621:Aminoisobutyric Acids / Q000494:pharmacology; D001692:Biological Transport; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D008715:Methionine / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D008781:Methyltyrosines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D014055:Tomography, Emission-Computed; D015899:Tomography, Emission-Computed, Single-Photon; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D000621:Aminoisobutyric Acids; D008781:Methyltyrosines; D019275:Radiopharmaceuticals; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; C017911:2-(methylamino)isobutyric acid; C030855:3-iodo-alpha-methyltyrosine; D008715:Methionine