3-O-Methyl-6-¹⁸F-Fluoro-L-DOPA (OMFD) Uptake via L- Amino Acid Transporter in Tumor Cells and Inflammatory Cells

System L amino acid transport is increased in various types of cancer. The new positron emission tomography (PET) tracer 3-O-methyl-6-¹⁸F-fluoro-L-DOPA (OMFD) is mainly accumulated via the system L and could serve to image cancer in vivo. However the differentiation between tumor and inflammatory reaction in tissues is often complicated. Therefore, we studied in vitro the accumulation mechanisms of OMFD in model systems of human tumors and inflammation, respectively. It is suggested that the high uptake of amino acid tracers is primarily caused by the higher transporter expression in tumors when compared to other tissues, e.g., inflammatory cells.
As previously shown, the subtype L-type amino acid transporter 1 (LAT1) is playing a key role of L amino acid transport in tumor cells. The functional LAT1 is a heterodimeric complex comprising a single membrane-spanning catalytic light chain protein (hLAT1) and the heavy chain of 4F2 antigen (h4F2hc), which are covalently linked via a disulfide bond.
For molecular characterization of L-type amino acid transporters focusing on the hLAT1-h4F2hc subtype quantitative RT-PCR was performed using the two different human tumor cell lines FaDu (squamous cell carcinoma) and HT-29 (colorectal adenocarcinoma). In comparison, phorbol ester stimulated THP-1 cells (a human monocyte/macrophage cell line) representing inflammatory cells were used. In vitro uptake assays were performed with HT-29, FaDu and THP-1 cells with OMFD under physiological amino acid concentrations.
OMFD demonstrated a saturable and sodium- and energy-independent accumulation in vitro in the different tumor cell lines, suggesting its uptake to be mediated mainly by sodium-independent LAT1. However, OMFD showed a significantly higher uptake in tumor cells when compared to inflammatory cells.
Our data demonstrate that OMFD could be a promising PET tracer for imaging of specific amino acid transport via LAT1 in tumors and, furthermore, for possible differentiation of tumorigenic from inflammatory processes. In conclusion, the identification and characterization of tumor specific amino acid transporters like LAT1 will be a helpful tool for diagnosis and therapy monitoring.