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Transport Mechanisms of 3-[¹²³I]Iodo--Methyl-L-Tyrosine in a Human Glioma Cell Line: Comparison with [³H-methyl]-L-Methionine

Institute of Medicine, Institute of Nuclear Chemistry, and Central Institute of Applied Mathematics, Research Center Jülich, Jülich
Clinic of Nuclear Medicine, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany

Correspondence: For correspondence or reprints contact: Karl-Josef Langen, MD, Institute of Medicine, Research Center Jülich GmbH, D-52425 Jülich, Germany.

ABSTRACT

The amino acid analog 3-[¹²³I]iodo--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°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. Conclusion: 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 ¹¹C-MET PET for the diagnostic evaluation of gliomas.

Key Words: amino acid transport • 3-[¹²³I]iodo--methyl-L-tyrosine • [³H-methyl]-L-methionine • glioma cells

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