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

食道癌患者のPETにおけるFluorine-18--Methyltyrosine(FAMT)取込みの生物学的重要性

鈴木 茂正*; 解良 恭一*; 大島 康宏; 石岡 典子; 宗田 真*; 横堀 武彦*; 宮崎 達也*; 織内 昇*; 富永 英之*; 金井 好克*; 塚本 憲史*; 浅尾 高行*; 対馬 義人*; 樋口 徹也*; 小山 徹也*; 桑野 博行*

Suzuki, Shigemasa*; Kaira, Kyoichi*; Ohshima, Yasuhiro; Ishioka, Noriko; Soda, Makoto*; Yokobori, Takehiko*; Miyazaki, Tatsuya*; Oriuchi, Noboru*; Tominaga, Hideyuki*; Kanai, Yoshikatsu*; Tsukamoto, Norifumi*; Asao, Takayuki*; Tsushima, Yoshito*; Higuchi, Tetsuya*; Oyama, Tetsunari*; Kuwano, Hiroyuki*

Fluorine-18--methyltyrosine (FAMT) as an amino acid tracer for positron emission tomography (PET) is useful for detecting human neoplasms. FAMT is accumulated in tumor cells solely via L-type amino acid transporter 1 (LAT1). This study was conducted to investigate the biological significance of FAMT uptake in patients with esophageal cancer. From April 2008 to December 2011, 42 patients with esophageal cancer underwent both FAMT PET and FDG PET before surgical treatment. The immunohistochemical analysis of LAT1, CD98, Ki-67, CD34, p53, p-Akt and p-mTOR was performed on the primary lesions. experiments were performed to examine the mechanism of FAMT uptake using LAT1 inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). High uptake of 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. experiments revealed that FAMT was specifically transported by LAT1. The uptake of FAMT within tumor cells is determined by the LAT1 expression and correlated with cell proliferation and angiogenesis in esophageal cancer. The present experiments also confirmed the presence of LAT1 as an underlying mechanism of FAMT accumulation.