Development of High specific reagents for BNCT

• Project/Area Number: 26461895
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Fukushima Medical University
• Principal Investigator: Tominaga Hideyuki 福島県立医科大学, 公私立大学の部局等, 准教授 (00393348)
• Co-Investigator(Kenkyū-buntansha): 織内 昇 福島県立医科大学, 公私立大学の部局等, 教授 (40292586)
• Research Collaborator: KANAI Yoshikatsu 大阪大学, 医学系研究科・薬理学, 教授
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: ホウ素 / BNCT / アミノ酸 / LAT1 / 腫瘍特異的 / トランスポーター / 腫瘍特異性 / がん特異性 / アミノ酸トランスポーター / 情報発信 / 中性子捕捉療法 / 陽電子断層撮像 / 薬剤集積解析

Outline of Final Research Achievements

Representative isoforms of L-type neutral amino acid transporter include LAT1 and LAT2, LAT1 is specific to cancer cells, and LAT2 is distributed in normal cells. There is also a difference in the transport amino acid substrate selectivity of both, while LAT 2 transports all neutral amino acids, whereas LAT 1 mainly transports large neutral amino acids (leucine, tyrosine, etc.).
Alpha-methyl tyrosine developed by us is an amino acid derivative with high selectivity for LAT1. I reported this usefulness during the research period. However, as a drug for boron neutron capture therapy, it was not possible to improve water solubility, and due to the introduction of a plurality of boron, drug development such as a decrease in selectivity of LAT 1 per se was not realized.

Research Products

• [Journal Article] Prognostic impact of LAT1 and CD98 expression in cutaneous angiosarcoma. (2017)
  • Author(s): Shimizu A, Kaira K, Okubo Y, Utsumi D, Yasuda M, Tominaga H, Oriuchi N, Kanai Y, Takahashi K, Ishikawa O.
  • Journal Title: Neoplasma Volume: 64 Issue: 02 Pages: 283-288
  • DOI: 10.4149/neo_2017_216
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Usefulness of 18F-α-Methyltyrosine PET for Therapeutic Monitoring of Patients with Advanced Lung Cancer. (2016)
  • Author(s): Kaira K, Higuchi T, Sunaga N, Arisaka Y, Hisada T, Tominaga H, Oriuchi N, Asao T, Tsushima Y, Yamada M.
  • Journal Title: Anticancer Res Volume: 36 Pages: 6481-6490
  • Peer Reviewed
• [Journal Article] Cardiac imaging with 18F-fluorodeoxyglucose PET/MRI in hypertrophic cardiomyopathy. (2016)
  • Author(s): Takeishi Y, Masuda A, Kubo H, Tominaga H, Oriuchi N, Takenoshita S.
  • Journal Title: J Nucl Cardiol Volume: -
  • Peer Reviewed
• [Journal Article] Efficacy of system l amino acid transporter 1 inhibition as a therapeutic target in esophageal squamous cell carcinoma. (2016)
  • Author(s): Ohshima Y, Kaira K, Yamaguchi A, Oriuchi N, Tominaga H, Nagamori S, Kanai Y, Yokobori T, Miyazaki T, Asao T, Tsushima Y, Kuwano H, Ishioka NS.
  • Journal Title: Cancer Sci. Volume: 107 Issue: 10 Pages: 1499-1505
  • DOI: 10.1111/cas.13021
  • Peer Reviewed / Open Access
• [Journal Article] Inflammatory involvement in a patient with Leriche syndrome evaluated by 18F-fluorodeoxyglucose PET/MRI. (2016)
  • Author(s): Masuda A, Yamaki T, Kunii H, Nemoto A, Kubo H, Tominaga H, Oriuchi N, Takenoshita S, Takeishi Y.
  • Journal Title: J Nucl Cardiol Volume: -
  • Peer Reviewed
• [Journal Article] Transport of 3-fluoro-l-α-methyl-tyrosine (FAMT) by organic ion transporters explains renal background in [(18)F]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 Issue: 2 Pages: 101-109
  • DOI: 10.1016/j.jphs.2016.01.001
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [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 Issue: 3 Pages: 347-352
  • DOI: 10.1111/cas.12878
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Structure-activity relations of leucine derivatives reveal critical moieties for cellular uptake and activation of mTORC1-mediated signaling. (2016)
  • Author(s): Nagamori S, Wiriyasermkul P, Okuda S, Kojima N, Hari Y, Kiyonaka S, Mori Y, Tominaga H, Ohgaki R, Kanai Y.
  • Journal Title: Amino Acids. Volume: 48 Issue: 4 Pages: 279-286
  • DOI: 10.1007/s00726-015-2158-z
  • Peer Reviewed / Acknowledgement Compliant
• [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. 2015 Volume: 7 Pages: 1161-1171
  • Peer Reviewed
• [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 Issue: 5 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 Issue: 4 Pages: 1175-1181
  • DOI: 10.1007/s12253-015-9954-3
  • 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. (2014)
  • 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: in press Issue: 9 Pages: 1014-1022
  • DOI: 10.1111/hepr.12431
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Expression of L-type amino acid transporter 1 (LAT1) as a prognostic and therapeutic indicator in multiple myeloma. (2014)
  • Author(s): Isoda A, Kaira K, Iwashina M, Oriuchi N, Tominaga H, Nagamori S, Kanai Y, Oyama T, Asao T, Matsumoto M, Sawamura M.
  • Journal Title: Cancer Sci. Volume: 105 Issue: 11 Pages: 1496-502
  • DOI: 10.1111/cas.12529
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] CD98 as a novel prognostic indicator for patients with stage III/IV hypopharyngeal squamous cell carcinoma. (2014)
  • Author(s): Toyoda M, Kaira K, Shino M, Sakakura K, Takahashi K, Takayasu Y, Tominaga H, Oriuchi N, Nikkuni O, Suzuki M, Iijima M, Tsukamoto N, Nagamori S, Kanai Y, Oyama T, Chikamatsu K.
  • Journal Title: Head Neck. Volume: in press Issue: 11 Pages: 1-6
  • DOI: 10.1002/hed.23797
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer. (2014)
  • Author(s): Toyoda M, Kaira K, Ohshima Y, Ishioka NS, Shino M, Sakakura K, Takayasu Y, Takahashi K, Tominaga H, Oriuchi N, Nagamori S, Kanai Y, Oyama T, Chikamatsu K.
  • Journal Title: Br J Cancer. Volume: 110 Issue: 10 Pages: 2506-13
  • DOI: 10.1038/bjc.2014.178
  • Peer Reviewed / Open Access
• [Journal Article] Biological significance of fluorine-18-α-methyltyrosine (FAMT) uptake on PET in patients with oesophageal cancer. (2014)
  • Author(s): Suzuki S, Kaira K, Ohshima Y, Ishioka NS, Sohda M, Yokobori T, Miyazaki T, Oriuchi N, Tominaga H, Kanai Y, Tsukamoto N, Asao T, Tsushima Y, Higuchi T, Oyama T, Kuwano H.
  • Journal Title: Br J Cancer Volume: Epub ahead of print Issue: 8 Pages: 1985-1991
  • DOI: 10.1038/bjc.2014.142
  • Peer Reviewed / Open Access
• [Journal Article] ASC amino-acid transporter 2 (ASCT2) as a novel prognostic marker in non-small cell lung cancer (2014)
  • Author(s): Shimizu K, Kaira K, Tomizawa Y, Sunaga N, Kawashima O, Oriuchi N, Tominaga H, Nagamori S, Kanai Y, Yamada M, Oyama T, Takeyoshi I
  • Journal Title: Br J Cancer Volume: Epub Issue: 8 Pages: 2030-2039
  • DOI: 10.1038/bjc.2014.88
  • Peer Reviewed / Open Access
• [Presentation] 福島県立医科大学 先端臨床研究センターの放射性薬剤への取り組み (2016)
  • Author(s): 富永英之、伊藤 浩、久保 均、原 孝光、南部武幸、竹之下誠一
  • Organizer: 第133回日本医学放射線学会 北日本地方会 第78回 日本核医学会 北日本地方会 合同会
  • Place of Presentation: 東北大学
  • Year and Date: 2016-10-24
• [Presentation] 3-fluoro-L--methyltyrosine (FAMT) PETにおける18F-FAMTの腎臓集積の分子機序の解明 (2015)
  • Author(s): Ling Wei, 富永英之, Pattama Wiriyasermkul, 大垣隆一, 萩原浩平, 奥田傑, 永森收志, 金井好克
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] がん細胞特異的アミノ酸トランスポーターLAT1を標的としたPETプローブの開発 (2014)
  • Author(s): 永森收志, 金井好克
  • Organizer: 第54回日本核医学会学術総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-11-06 – 2014-11-09
  • Invited
• [Presentation] [14C]-L-FAMTを用いた腫瘍細胞型アミノ酸トランスポーター LAT1の活性測定法の開発 (2014)
  • Author(s): 富永英之, Ling Wei, 織内昇, Pattama Wiriyasermkul, 大垣隆一, 永森收志, 金井好克, 伊藤浩, 宇川義一, 宍戸文男, 竹之下誠一
  • Organizer: 第54回日本核医学会学術総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-11-06 – 2014-11-09
• [Presentation] がん細胞型アミノ酸トランスポーター LAT1と がんの診断と治療 (2014)
  • Author(s): 金井好克
  • Organizer: 第11回 日本中性子捕捉療法学会
  • Place of Presentation: 大阪大学
  • Year and Date: 2014-07-05 – 2014-07-06
  • Invited