Monitoring of amino acid transporter targeted therapy with 18F-FAMT PET

• Project/Area Number: 25461801
• 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 (2015); Gunma University (2013-2014)
• Principal Investigator: oriuchi noboru 福島県立医科大学, 公私立大学の部局等, 教授 (40292586)
• Co-Investigator(Kenkyū-buntansha): TOMINAGA Hideyuki 福島県立医科大学, 先端臨床医研究センター, 准教授 (00393348) ; KAIRA Kyouichi 群馬大学大学院医学系研究科, がん治療臨床開発学講座, 教授 (40400783) ; OSHIMA Yasuhiro 量子科学技術研究開発機構, 量子ビーム科学研究部門, 博士研究員 (00588676)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: LAT1 / アミノ酸トランスポーター / ポジトロンCT / 18F-FAMT / 分子標的治療 / PET / コンパニオン診断 / ASCT2 / 胆管細胞がん / 胆管がん / mTOR

Outline of Final Research Achievements

The present studies disclosed roles of L-type amino acid transporter 1 (LAT1) for growth and prognosis in a variety of cancer, suggesting that LAT1 would be a molecular target of anti-cancer therapy. Clinical significance of L-[3-18F]-α-methyl tyrosine (18F-FAMT) PET have been examined. 18F-FAMT is accumulated in tumor specifically via LAT1, therefore, 18F-FAMT PET would be a marker of LAT1 expression. Uptake of 18F-FAMT could differentiate between benign lesions and malignant tumors. Additionally, the high uptake of 18F-FAMT could predict poor outcome of patients. 18F-FAMT PET would be an imaging marker of LAT1-targeted therapy.
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 decreased proliferation of cells and growth of xenograft in nude mice.　Moreover, prognostic potential of ASC amino-acid transporter 2 (ASCT2) have been shown in biliary tract cancers.

Research Products

• [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] 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 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] 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] Clinicopathological significance of ASC amino acid transporter-2 expression in pancreatic ductal carcinoma. (2015)
  • Author(s): Kaira K, Sunose Y, Arakawa K, Sunaga N, Shimizu K, Tominaga H, Oriuchi N, Nagamori S, Kanai Y, Oyama T, Takeyoshi I.
  • Journal Title: Histopathology. Volume: 66 Issue: 2 Pages: 234-43
  • DOI: 10.1111/his.12464
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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] Biological significance of 18F-FDG uptake on PET in patients with non-small-cell lung cancer. (2014)
  • Author(s): Kaira K, Serizawa M, Koh Y, Takahashi T, Yamaguchi A, Hanaoka H, Oriuchi N, Endo M, Ohde Y, Nakajima T, Yamamoto N.
  • Journal Title: Lung Cancer Volume: 83 Issue: 2 Pages: 197-204
  • DOI: 10.1016/j.lungcan.2013.11.025
  • Peer Reviewed
• [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
• [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] 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] 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] CD98 is a promising prognostic biomarker in biliary tract cancer. (2014)
  • Author(s): Kaira K, Sunose Y, Oriuchi N, Kanai Y, Takeyoshi I.
  • Journal Title: Hepatobiliary Pancreat Dis Int. Volume: 13 Issue: 6 Pages: 654-7
  • DOI: 10.1016/s1499-3872(14)60278-2
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Biological evaluation of 3-[18F]fluoro-α-methyl-D-tyrosine (D-[18F]FAMT) as a novel amino acid tracer for positron emission tomography. (2013)
  • Author(s): Ohshima Y
  • Journal Title: Ann Nucl Med Volume: 27 Issue: 4 Pages: 314-324
  • DOI: 10.1007/s12149-013-0687-7
  • Peer Reviewed
• [Journal Article] Clinicopathological significance of L-type amino acid transporter 1 (LAT1) expression in patients with adenoid cystic carcinoma. (2013)
  • Author(s): Kaira K, Toyoda M, Shino M, Sakakura K, Takahashi K, Tominaga H, Oriuchi N, Kanai Y, Oyama T, Chikamatsu K.
  • Journal Title: Pathol. Oncol. Res. Volume: 19 Issue: 4 Pages: 649-656
  • DOI: 10.1007/s12253-013-9624-2
  • Peer Reviewed
• [Journal Article] Diagnostic usefulness of F-FAMT PET and L-type amino acid transporter 1 (LAT1) expression in oral squamous cell carcinoma. (2013)
  • Author(s): Nobusawa A, Kim M, Kaira K, Miyashita G, Negishi A, Oriuchi N, Higuchi T, Tsushima Y, Kanai Y, Yokoo S, Oyama T.
  • Journal Title: Eur J Nucl Med Mol Volume: 40 Issue: 11 Pages: 1692-1700
  • DOI: 10.1007/s00259-013-2477-9
  • Peer Reviewed
• [Journal Article] Clinical significance of L-type amino acid transporter 1 expression as a prognostic marker and potential of new targeting therapy in biliary tract cancer (2013)
  • Author(s): Kaira K, Sunose Y, Ohshima Y, Ishioka NS, Arakawa K, Ogawa T, Sunaga N, Shimizu K, Tominaga H, Oriuchi N, Itoh H, Nagamori S, Kanai Y, Yamaguchi A, Segawa A, Ide M, Mori M, Oyama T, Takeyoshi I
  • Journal Title: BMC Cancer Volume: 16 Issue: 1 Pages: 482-482
  • DOI: 10.1186/1471-2407-13-482
  • Peer Reviewed
• [Presentation] 胆管癌における新規治療標的としてのLAT1の可能性についての検討 (2014)
  • Author(s): 大島康宏、富永英之、永森収志、金井好克、織内 昇、石岡典子
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] FDG-PETで奇静脈浸潤が認められた食道癌の1症例 (2014)
  • Author(s): 織内 昇、清水淳史、友利彰寿、森主達夫、宮田佳典
  • Organizer: 第68回日本食道学会学術集会
  • Place of Presentation: 東京ドームホテル（東京都）
  • Year and Date: 2014-07-03 – 2014-07-04
• [Presentation] アミノ酸トランスポーターLAT1の臨床病理学的意義ならびに画像マーカーの開発 (2013)
  • Author(s): 織内 昇
  • Organizer: 第51回 日本癌治療学会学術集会
  • Place of Presentation: 京都市