Application of F-18-FMT PET for amino acid transporter targetedcancer therapy

• Project/Area Number: 22300334
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor diagnosis
• Research Institution: Gunma University
• Principal Investigator: ORIUCHI Noboru 群馬大学, 大学院・医学系研究科, 客員教授 (40292586)
• Co-Investigator(Kenkyū-buntansha): TOMINAGA Hideyuki 群馬大学, 大学院・医学系研究科, 寄附講座教員 (00393348) ; KANAI Yoshikatsu 大阪大学, 大学院・医学系研究科, 教授 (60204533)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2011: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2010: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
• Keywords: LAT1 / 肺がん / ^<18>F-FAMT / PET / 膵がん / アミノ酸トランスポーター / F-18-FAMT / 18F-FAMT / 非小細胞肺癌 / BCH

Research Abstract

Expression of amino acid transporter LAT1 was correlated with pathological malignancy and prognosis of patients with non-small cell lung cancer andpancreas cancer. LAT1 specific ^<18>F-FMT uptake in the tumor was correlated with therapeutic effect and was an independent prognostic marker.
LAT1 inhibitor suppressed both amino acid trans ancercells in vitro, and also suppressed tumor coincidedwith decreased ^<18>F-FMT uptake.
port and proliferation of these cgrowth in animal models which was These results indicated possible LAT1-targeted cancer therapy and use of ^<18>F-FMT PET as a surrogate marker.

Research Products

• [Journal Article] Biological evaluation of 3-[^<18>F]fluoro-α-methyl-D-tyrosine (D-[^<18>F]FAMT) as a novel amino acidtracer for positron emissiontomography (2013)
  • Author(s): Ohshima Y, Hanaoka H, Tominaga H, KanaiY, Kaira K, Yamaguchi A, Nagamori S, Oriuchi N, Tsushima Y, Endo K, Ishioka NS
  • Journal Title: Ann Nucl Med Volume: 27 Pages: 314-324
• [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] Prognostic significance of L-type amino-acid transporter 1expression in surgically resected pancreatic cancer (2012)
  • Author(s): Kaira K, Sunose Y, Arakawa K, Ogawa T, Sunaga N, Shimizu K, Tominaga H, Oriuchi N, Itoh H,Nagamori S, Kanai Y, Segawa A, Furuya M, Mori M, Oyama T, Takeyoshi I
  • Journal Title: Br J Cancer Volume: 107 Pages: 632-638
• [Journal Article] Transport of 3-Fluoro-L-α-Methyl-Tyrosine by Tumor-Upregulated L-Type Amino Acid Transporter 1: A Cause of the Tumor Uptake in PET (2012)
  • Author(s): Wiriyasermkul P, Nagamori S, TominagaH, Oriuchi N, Kaira K, Nakao H,Kitashoji T, Ohgaki R, Tanaka H, EndouH, Endo K, Sakurai H, Kanai Y
  • Journal Title: J Nucl Med Volume: 53 Pages: 1253-1261
• [Journal Article] Prognostic significance of L-type amino-acid transporter 1 expression in surgically resected pancreatic cancer. (2012)
  • Author(s): Kaira K
  • Journal Title: Br J Cancer Volume: 107 Issue: 4 Pages: 632-638
  • DOI: 10.1038/bjc.2012.310
  • Peer Reviewed
• [Journal Article] L-type amino acidtransporter 1 (LAT1) expression inmalignant pleural mesothelioma (2011)
  • Author(s): Kaira K, Oriuchi N, Takahashi T, Nakagawa K, Ohde Y,Okumura T, MurakamiH, Shukuya T, Kenmotsu H, Naito T,Kanai Y, Endo M, Kondo H, Nakajima T, Yamamoto N
  • Journal Title: Anticancer Res Volume: 31 Pages: 4075-82
• [Journal Article] Relationship between LAT1 Expression and Response toPlatinum-based Chemotherapy in Non-small Cell Lung Cancer Patients with Postoperative Recurrence (2011)
  • Author(s): Kaira K, Takahashi T, Murakami H, Shukuya T, Kenmotsu H,Naito T, OriuchiN, Kanai Y, Endo M, Kondo H, Nakajima T, Yamamoto N
  • Journal Title: Anticancer Res Volume: 31 Pages: 3775-3782
• [Journal Article] LAT1 expression is closelyassociated with hypoxic markers and mTOR in resected non-small cell lung cancer (2011)
  • Author(s): Kaira K, Oriuchi N, Takahashi T, Nakagawa K, Ohde Y,Okumura T, MurakamiH, Shukuya T, Kenmotsu H, Naito T,Kanai Y, Endo M, Kondo H, Nakajima T, Yamamoto N
  • Journal Title: Am J Transl Res Volume: 3 Pages: 468-478
• [Journal Article] Preparation and biological evaluation of 3-[76Br]bromo-α-methyl-L-tyrosine, a novel tyrosine analog for positronemission tomography imaging of tumors (2011)
  • Author(s): Ohshima Y, Hanaoka H, Watanabe S, Sugo Y, Watanabe S, Tominaga H, Oriuchi N, Endo K, Ishioka NS
  • Journal Title: Nucl Med Biol Volume: 38 Pages: 857-865
• [Journal Article] Prognostic significance of L-type amino acid transporter 1 (LAT1) and 4F2 heavychain (CD98) expression in surgically resectable stage III non-small cell lung cancer (2010)
  • Author(s): Kaira K, Oriuchi N, Imai H, Shimizu K, Yanagitani N, Sunaga N, Hisada T, Kawashima O, Kameda Y, Ishizuka T,Kanai Y, Nakajima T, Mori M
  • Journal Title: Exp Ther Med Volume: 1 Pages: 799-808
• [Journal Article] ^<18>F-FAMT-PET is useful forthe diagnosis of lymph node metastasis in operable esophageal squamous cell carcinoma (2010)
  • Author(s): Sohda M, Kato H, Suzuki S, Tanaka N, Sano A, Sakai M, Inose T, Nakajima M, Miyazaki T, Fukuchi M, Oriuchi N, Endo K, Kuwano H
  • Journal Title: Ann Surg Oncol Volume: 17 Pages: 3181-3186
• [Journal Article] Inhibition of L-type amino acidtransporter 1 has antitumor activity in non-small cell lung cancer (2010)
  • Author(s): Imai H, Kaira K, Oriuchi N, Shimizu K, Tominaga H, Yanagitani N, Sunaga N, Ishizuka T, Nagamori S, Promchan K, Nakajima T, Yamamoto N, Mori M, Kanai Y
  • Journal Title: Anticancer Res Volume: 30 Pages: 4819-4828
• [Journal Article] Comparison of L-type amino acid transporter 1 expression and L-[3-^<18>F]-α-methyl tyrosineuptake in outcome of non-small cell lung cancer (2010)
  • Author(s): Kaira K, Oriuchi N, Shimizu K, Imai H, Tominaga H, Yanagitani N, Sunaga N, Hisada T, Ishizuka T,Kanai Y, Oyama T,Mori M, Endo K
  • Journal Title: Nucl Med Biol Volume: 37 Pages: 911-916
• [Journal Article] Assessment of Therapy Response in LungCancer with Fluorine-18-α-Methyltyrosine Positron Emission Tomography (2010)
  • Author(s): Kaira K, Oriuchi N, Yanagitani N, Sunaga N, Ishizuka T, Mori M, Endo K
  • Journal Title: AJR Volume: 195 Pages: 1204-1211
• [Journal Article] ^<18>F-FAMT uptake correlates with tumor proliferative activity in oral squamous cell carcinoma: comparative study with ^<18>F-FDG PET andimmunohistochemistry (2010)
  • Author(s): Miyashita G, Higuchi T, Oriuchi N, Arisaka Y, Hanaoka H, Tominaga H, Morita S, Miyakubo M, Ishikita T, Nakasone Y, Negishi A, Yokoo S, Endo K
  • Journal Title: Ann Nucl Med Volume: 24 Pages: 579-584
• [Journal Article] Inhibition of L-type amino acid transporter 1 has antitumor activity in non-small cell lung cancer. (2010)
  • Author(s): Imai H
  • Journal Title: Anticancer Res Volume: 30 Pages: 4819-4828
  • Peer Reviewed
• [Journal Article] Comparison of L-type amino acid transporter 1 expression and L-[3-^<18>F]-α-methyl tyrosine uptake in outcome of non-small cell lung cancer. (2010)
  • Author(s): Kaira K
  • Journal Title: Nucl Med Biol Volume: 37 Pages: 911-916
  • Peer Reviewed
• [Journal Article] Assessment of Therapy Response in Lung Cancer with Fluorine-18-α-Methyltyrosine Positron Emission Tomography. (2010)
  • Author(s): Kaira K
  • Journal Title: AJR Volume: 195 Pages: 1204-1211
  • Peer Reviewed
• [Journal Article] ^<18>F-FAMT uptake correlates with tumor proliferative activity in oral squamous cell carcinoma : comparative study with ^<18>F-FDG PET and immunohistochemistry.? (2010)
  • Author(s): Miyashita G
  • Journal Title: Ann Nucl Med Volume: 24 Pages: 579-584
  • Peer Reviewed
• [Journal Article] Additional value of integrated PET/CT over PET alone in the initial staging and follow up of head and neck malignancy.? (2010)
  • Author(s): Ishikita T
  • Journal Title: Ann Nucl Med Volume: 24 Pages: 77-82
  • Peer Reviewed
• [Journal Article] Biologic correlation of 2-[^<18>F]-fluoro-2-deoxy-D-glucose uptake on positron emission tomography in thymic epithelial tumors.? (2010)
  • Author(s): Kaira K
  • Journal Title: J Clin Oncol Volume: 28 Pages: 3746-3753
  • Peer Reviewed
• [Presentation] Clinical significance of [^<18>F]-α-methyl tyrosine PET as a potential surrogate marker of LAT1 expression for predicting prognosis of non-smallcell lung cancer (2010)
  • Author(s): Oriuchi N, Kaira K, Shimizu K, et al
  • Organizer: American Society of Clinical Oncology
  • Place of Presentation: Chicago, USA
  • Year and Date: 2010-06-05
• [Presentation] Clinical significance of [^<18>F]-α-methyl tyrosine PET as a potential surrogate marker of LAT1 expression for predicting prognosis of non-small cell lung cancer. (2010)
  • Author(s): Oriuchi N
  • Organizer: American Society of Clinical Oncology
  • Place of Presentation: Chicago, USA
  • Year and Date: 2010-06-05
• [Book] ^<18>F-FDG、^<18>F-FAMT PE T:グルコーストランスポーター・アミノ酸トランスポーターを標的とした癌診断.金井好克 編.トランスポートソーム . 生体膜輸送機構の全体像に迫る (2011)
  • Author(s): 織内 昇
  • Publisher: 遺伝子医学MOOK19.株式会社メディカルドゥ, 大阪
• [Book] 2. アミノ酸および誘導体分子プローブとそのイメージング.米倉義春、伊藤正敏, 他 編.臨床医とコメディカルのための最新クリニカルPET (2010)
  • Author(s): 織内 昇
  • Publisher: 先端医療技術研究所