Biological significance of fluorine-18-α-methyltyrosine (FAMT) uptake on PET in patients with oesophageal cancer

Purpose: F-18-FAMT as an amino-acid tracer for positron emission tomography (PET) is useful for detecting human neoplasms. F-18-FAMT is accumulated in tumour cells solely via L-type amino-acid transporter 1 (LAT1). This study was conducted to investigate the biological significance of F-18-FAMT uptake in patients with oesophageal cancer. Methods: From April 2008 to December 2011, 42 patients with oesophageal cancer underwent both F-18-FAMT PET/CT and F-18-FDG PET/CT before surgical treatment. The immunohistochemical analysis of LAT1, CD98, Ki-67, CD34, p53, p-Akt and p-mTOR was performed on the primary lesions. In vitro experiments were performed to examine the mechanism of F-18-FAMT uptake. Results: High uptake of F-18-FAMT was significantly associated with advanced stage, lymph node metastasis and the expression of LAT1, CD98, Ki-67 and CD34. LAT1 expression yielded a statistically significant correlation with CD98 expression, cell proliferation, angiogenesis and glucose metabolism. In vitro experiments revealed that F-18-FAMT was specifically transported by LAT1. Conclusions: The uptake of F-18-FAMT within tumour cells is determined by the LAT1 expression and correlated with cell proliferation and angiogenesis in oesophageal cancer. The present experiments also confirmed the presence of LAT1 as an underlying mechanism of F-18-FAMT accumulation.