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3-O-Methyl-6-¹⁸F-Fluoro-L-Dopa, a New Tumor Imaging Agent: Investigation of Transport Mechanism In Vitro

¹ Institut fuer Bioanorganische und Radiopharmazeutische Chemie, PET Zentrum Rossendorf, Forschungszentrum Rossendorf, Dresden, Germany
² Klinik und Poliklinik fuer Nuklearmedizin, Technische Universitaet Dresden und PET Zentrum Rossendorf, Dresden, Germany

¹⁸F-Labeled amino acids represent a promising class of imaging agents in tumors, particularly brain tumors. However, the determination of their potential to image peripheral tumors, possibly depending on individual transport characteristics, still remains an area of investigation. The present study investigated the transport mechanism for 3-O-methyl-6-¹⁸F-fluoro-L-dopa (OMFD), a novel ¹⁸F-labeled phenylalanine derivative, into tumor cells. Methods: OMFD has routinely and reliably been prepared for clinical use in 20%–25% radiochemical yield (decay corrected, related to ¹⁸F-F₂) using 6-¹⁸F-fluoro-L-3,4-dihydroxyphenylalanine preparation devices with minor modifications. In vitro uptake assays with HT-29 (human colon adenocarcinoma) cells, FaDu (squamous cell carcinoma) cells, and RBE4 (immortalized rat brain endothelial) cells were performed with OMFD under physiologic amino acid concentrations without and with the competitive transport inhibitors 2-aminobicyclo-[2,2,1]-heptane-2-carboxylic acid and -(methylamino)isobutyric acid plus serine and without or with Na⁺. Results: Transport inhibition experiments using specific competitive inhibitors demonstrated that uptake of OMFD in all cell lines tested was mediated mainly by the sodium-independent high-capacity amino acid transport systems. The highest OMFD uptake was in FaDu cells. Conclusion: OMFD seems to be a promising PET tracer for imaging of amino acid transport in tumors.

Key Words: amino acid transport • ¹⁸F • PET • radiotracer

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