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

Biological significance of fluorine-18-α-methyltyrosine (FAMT) uptake on PET in patients with oesophageal cancer.
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DOI:
10.1038/bjc.2014.142
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发表时间:
2014-04-15
影响因子:
8.8
通讯作者:
Kuwano, H.
Kuwano, H.
中科院分区:
医学1区
文献类型:
--
作者:
Suzuki, S.;Kaira, K.;Ohshima, Y.;Ishioka, N. S.;Sohda, M.;Yokobori, T.;Miyazaki, T.;Oriuchi, N.;Tominaga, H.;Kanai, Y.;Tsukamoto, N.;Asao, T.;Tsushima, Y.;Higuchi, T.;Oyama, T.;Kuwano, H.

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18F-FAMT 作为正电子发射断层扫描 (PET) 的氨基酸示踪剂,可用于检测人类肿瘤。 18F-FAMT 仅通过 L 型氨基酸转运蛋白 1 (LAT1) 在肿瘤细胞中积累。本研究旨在探讨食管癌患者摄取 18F-FAMT 的生物学意义。 2008年4月至2011年12月,42例食管癌患者在手术治疗前同时接受了~(18)F-FAMT PET/CT和~(18)F-FDG PET/CT检查。对原发病灶进行LAT1、CD98、Ki-67、CD34、p53、p-Akt和p-mTOR的免疫组化分析。进行体外实验来检查 18F-FAMT 摄取的机制。 18F-FAMT 的高摄取与晚期、淋巴结转移以及 LAT1、CD98、Ki-67 和 CD34 的表达显着相关。 LAT1 表达与 CD98 表达、细胞增殖、血管生成和葡萄糖代谢具有统计学显着相关性。体外实验表明 18F-FAMT 由 LAT1 特异性转运。肿瘤细胞内 18F-FAMT 的摄取由 LAT1 表达决定,并与食管癌中的细胞增殖和血管生成相关。本实验还证实了 LAT1 的存在是 18F-FAMT 积累的潜在机制。
18F-FAMT as an amino-acid tracer for positron emission tomography (PET) is useful for detecting human neoplasms. 18F-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 18F-FAMT uptake in patients with oesophageal cancer. From April 2008 to December 2011, 42 patients with oesophageal cancer underwent both 18F-FAMT PET/CT and 18F-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 18F-FAMT uptake. High uptake of 18F-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 18F-FAMT was specifically transported by LAT1. The uptake of 18F-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 18F-FAMT accumulation.
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