LAT1 (SLC7A9) is a large-neutral amino acid transporter that forms heterodimer with CD98hc to function at the plasma membrane. LAT1 is a target for cancer diagnosis and therapy due to its important roles on cancer cell growth. PET imaging using FDG is a common cancer diagnosis. Yet, high accumulation of FDG in inflammatory lesions causes false positive results. In contrast, we and others reported that LAT1 selective PET tracers including ¹⁸F-FAMT (3-fluoro-L-a-methyl-tyrosine) were highly accumulated in tumors but not in inflammatory lesions.
Here, we demonstrated that FAMT was taken up by tumors but not by inflammatory lesions in animal models indicating no LAT1 function in inflammatory lesions, despite similar LAT1 expression in tumors and inflammatory lesions. LAT1 formed complex with CD98hc at the plasma membrane in tumors. However, LAT1 retained as monomer inside the cells of inflammatory lesions while CD98hc existed as dimer. Membrane proteome showed other SLC7 transporters in the inflammatory lesions whereas LAT1 dominated in tumor. Taken all together, in inflammatory lesions unlike tumors, LAT1 exists as a monomer inside of the cells and has no function at the plasma membrane, and likelihood CD98hc forms complex with SLC7 family beside LAT1. Our results suggest the different roles of LAT1 in tumors and inflammatory lesions.