PETによるアミノ酸トランスポータ標的がん治療のモニタリング法の開発に関する研究

2015 Fiscal Year Annual Research Report

• Project/Area Number: 25461801
• Research Institution: Fukushima Medical University
• Principal Investigator: 織内 昇 福島県立医科大学, 公私立大学の部局等, 教授 (40292586)
• Co-Investigator(Kenkyū-buntansha): 富永 英之 福島県立医科大学, 公私立大学の部局等, 准教授 (00393348) ; 大島 康宏 国立研究開発法人日本原子力研究開発機構, その他部局等, 研究員 (00588676) ; 解良 恭一 群馬大学, 医学(系)研究科(研究院), その他 (40400783)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: LAT1 / 18F-FAMT / PET

Outline of Annual Research Achievements

Clinical significance of L-type amino acid transporter 1 (LAT1) expression was achieved in this research. Clinicopathological studies disclosed vital roles of LAT1 for the growth and prognosis in a variety of cancer including biliary tract cancer by in vitro experiment, animal studies, and clinical examination. These data suggest that LAT1 would be a molecular target of anti-cancer therapy of cancer.
Clinical significance of L-[3-18F]-α-methyl tyrosine (18F-FAMT) PET have been examined in various human cancers. 18F-FAMT is accumulated in tumor specifically via LAT1. Uptake of 18F-FAMT within tumor cells is useful for differentiating between benign lesions and malignant tumors. Additionally, the high uptake of 18F-FAMT is a promising marker for predicting poor outcome of patients. 18F-FAMT PET would be an imaging marker of LAT1-targeted therapy.
In vivo experiments revealed that LAT1 inhibitor 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) inhibited [14C] L-leucine uptake in human cholangiocarcinoma cell line named HuCCT1, and significantly decreased proliferation of HuCCT1 cells in a concentration dependent manner, and also showed significant delay in the growth of HuCCT1 xenograft in nude mice without showing significant changes in the body weight of these mice.
Moreover, other amino acid transporters have been evaluated. Possibility of prognostic potential of ASC amino-acid transporter 2 (ASCT2) have been shown in cancers originated from biliary tract.

Research Products

• [Journal Article] Transport of 3-fluoro-l-α-methyl-tyrosine (FAMT) by organic ion transporters explains renal background in [18F]FAMT positron emission tomography. (2016)
  • Author(s): Wei L, Tominaga H, Ohgaki R, Wiriyasermkul P, Hagiwara K, Okuda S, Kaira K, Kato Y, Oriuchi N, Nagamori S, Kanai Y.
  • Journal Title: J Pharmacol Sci Volume: 130 Pages: 101-109
  • DOI: 10.1016/j.jphs.2016.01.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Specific transport of 3-fluoro-l-α-methyl-tyrosine by LAT1 explains its specificity to malignant tumors in imaging. (2016)
  • Author(s): Wei L, Tominaga H, Ohgaki R, Wiriyasermkul P, Hagiwara K, Okuda S, Kaira K, Oriuchi N, Nagamori S, Kanai Y.
  • Journal Title: Cancer Sci Volume: 107 Pages: 347-352
  • DOI: 10.1111/cas.12878
  • Open Access / Int'l Joint Research
• [Journal Article] Prognostic significance of L-type amino acid transporter 1 (LAT1) expression in patients with ovarian tumors. (2015)
  • Author(s): Kaira K, Nakamura K, Hirakawa T, Imai H, Tominaga H, Oriuchi N, Nagamori S, Kanai Y, Tsukamoto N, Oyama T, Asao T, Minegishi T.
  • Journal Title: Am J Transl Res Volume: 7 Pages: 1161-1171
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prognostic significance of L-type amino acid transporter 1 (LAT1) expression in cutaneous melanoma. (2015)
  • Author(s): Shimizu A, Kaira K, Kato M, Yasuda M, Takahashi A, Tominaga H, Oriuchi N, Nagamori S, Kanai Y, Oyama T, Asao T, Ishikawa O.
  • Journal Title: Melanoma Res Volume: 25 Pages: 399-405
  • DOI: 10.1097/CMR.0000000000000181
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expression of Amino Acid Transporters (LAT1 and ASCT2) in Patients with Stage III/IV Laryngeal Squamous Cell Carcinoma. (2015)
  • Author(s): Nikkuni O, Kaira K, Toyoda M, Shino M, Sakakura K, Takahashi K, Tominaga H, Oriuchi N, Suzuki M, Iijima M, Asao T, Nishiyama M, Nagamori S, Kanai Y, Oyama T, Chikamatsu K.
  • Journal Title: Pathol Oncol Res Volume: 21 Pages: 1175-1181
  • DOI: 10.1007/s12253-015-9954-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Relationship between CD147 and expression of amino acid transporters (LAT1 and ASCT2) in patients with pancreatic cancer. (2015)
  • Author(s): Kaira K, Arakawa K, Shimizu K, Oriuchi N, Nagamori S, Kanai Y, Oyama T, Takeyoshi I.
  • Journal Title: Am J Transl Res Volume: 7 Pages: 356-363
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expression of amino acid transporters (LAT1, ASCT2 and xCT) as clinical significance in hepatocellular carcinoma. (2015)
  • Author(s): Namikawa M, Kakizaki S, Kaira K, Tojima H, Yamazaki Y, Horiguchi N, Sato K, Oriuchi N, Tominaga H, Sunose Y, Nagamori S, Kanai Y, Oyama T, Takeyoshi I, Yamada M.
  • Journal Title: Hepatol Res Volume: 45 Pages: 1014-1022
  • DOI: 10.1111/hepr.12431
  • Peer Reviewed / Open Access / Int'l Joint Research