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PET Molecular Imaging for the molecular targeted cancer therapy focused on EGFR for personalized Medicine

Research Project

Project/Area Number 16H05397
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionNational Institutes for Quantum and Radiological Science and Technology

Principal Investigator

NISHII RYUICHI  国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 分子イメージング診断治療研究部, 主幹研究員(定常) (60463212)

Co-Investigator(Kenkyū-buntansha) 加川 信也  滋賀県立総合病院(研究所), 画像研究部門, 主任研究員 (10393191)
川井 恵一  金沢大学, 保健学系, 教授 (30204663)
小川 数馬  金沢大学, 新学術創成研究機構, 教授 (30347471)
東 達也  国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 分子イメージング診断治療研究部, 部長(定常) (50324629)
木村 寛之  京都薬科大学, 薬学部, 准教授 (50437240)
水谷 陽一  宮崎大学, 医学部, 助教 (40599586)
小川 衣未 (松本衣未)  宮崎大学, 医学部, その他 (70752723)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Keywords癌 / 画像診断 / PETイメージング / 分子イメージング / EGFR / がん / 放射線 / トランスレーショナルリサーチ / 個別化医療
Outline of Final Research Achievements

We have developed diagnostic imaging agents focusing on tyrosine kinases of the epidermal growth factor receptors, which are strictly related to cancer cell proliferation, angiogenesis, induction of invasion and metastasis, and apoptosis. We succeeded in synthesizing several new imaging radiopharmaceuticals with high EGFR-TK inhibitory activity. After confirming the tyrosine kinase inhibitory affinity for each agent in the biological assay experiments, we have performed imaging studies that have high EGFR-TK inhibitory activity in cancer-bearing mice. PET imaging experiments in cancer-bearing mice were used to visualize mutant EGFR-expressing tumor cells and analyze their pharmacokinetics. PET imaging of EGFR inhibitor-loaded mice was also performed. Furthermore, specific organ accumulation, excretion, and blood clearance of the drug were evaluated to determine its potential for clinical application.

Academic Significance and Societal Importance of the Research Achievements

本研究で開発する画像診断は、治療前にEGFR-TK阻害剤適応患者を選別することで、分子標的薬による副作用の危険性を回避すると共に的確な治療戦略決定に寄与する。またEGF受容体の発現と活性度の定量的画像解析法によりEGFR-TK阻害剤の治療効果予測・予後予測も可能となり、種々の分子標的治療にも応用可能な画像診断として期待できる。
さらには画像診断情報を基にした個々の体質に合わせた予防・治療を可能とする効果的・効率的な個別化医療(オーダーメイド医療)の実現に寄与できると共に、癌の増殖メカニズムとその診断・治療という臨床をつなぐ癌のトランスレーショナルリサーチの一翼を強力に推進することが期待される。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (17 results)

All 2020 2019 2018 2017 2016

All Journal Article (17 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 16 results,  Open Access: 9 results,  Acknowledgement Compliant: 1 results)

  • [Journal Article] Transport mechanism and affinity of [99mTc]mercaptoacetyltriglycine ([99mTc]MAG3) on the apical membrane of renal proximal tubule cells.2020

    • Author(s)
      Kobayashi M, Nishi K, Mizutani A, Okudaira H, Nakanishi T, Shikano N, Nishii R, Tamai I, Kawai K.
    • Journal Title

      Nuclear Medicine and Biology.

      Volume: 84-85 Pages: 33-37

    • DOI

      10.1016/j.nucmedbio.2020.01.002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Nucleoside Derivative 5-Vinyluridine (VrU) for Imaging RNA in Cells and Animals2019

    • Author(s)
      Liu Hong-shan、Ishizuka Takumi、Kawaguchi Makiko、Nishii Ryuichi、Kataoka Hiroaki、Xu Yan
    • Journal Title

      Bioconjugate Chemistry

      Volume: 30 Issue: 11 Pages: 2958-2966

    • DOI

      10.1021/acs.bioconjchem.9b00643

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Imaging of Hepatic Drug Transporters with [131I]6-β-iodomethyl-19-norcholesterol.2019

    • Author(s)
      Kobayashi M., Nishi K., Mizutani A., Hokama T., Matsue M., Tsujikawa T., Nakanishi T., Nishii R., Tamai I., Kawai K.
    • Journal Title

      Sci. Rep.

      Volume: 9 Issue: 1 Pages: 13413-13413

    • DOI

      10.1038/s41598-019-50049-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of transporter-mediated hepatobiliary transport of newly developed 18F-labeled pitavastatin derivative, PTV-F1, in rats by PET imaging2019

    • Author(s)
      Kimura Hiroyuki、Yagi Yusuke、Mikamo Mutsumi、Maeda Kazuya、Kagawa Shinya、Arimitsu Kenji、Higashi Tatsuya、Nishii Ryuichi、Ono Masahiro、Nakamoto Yuji、Togashi Kaori、Kusuhara Hiroyuki、Saji Hideo
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 34 Issue: 5 Pages: 317-324

    • DOI

      10.1016/j.dmpk.2019.05.006

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Design, synthesis, and biological evaluation of radioiodinated benzo[d]imidazole-quinoline derivatives for platelet-derived growth factor receptor β (PDGFRβ) imaging2019

    • Author(s)
      Effendi Nurmaya、Mishiro Kenji、Takarada Takeshi、Yamada Daisuke、Nishii Ryuichi、Shiba Kazuhiro、Kinuya Seigo、Odani Akira、Ogawa Kazuma
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 27 Issue: 2 Pages: 383-393

    • DOI

      10.1016/j.bmc.2018.12.016

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 1.The pharmacological properties of 3-arm or 4-arm DOTA constructs for conjugation to α-melanocyte-stimulating hormone analogues for melanoma imaging2018

    • Author(s)
      Kobayashi M, Kato T, Washiyama K, Ihara M, Mizutani A, Nishi K, Flores LG 2nd, Nishii R, Kawai K.
    • Journal Title

      PLoS One

      Volume: 14 Issue: 3 Pages: e0213397-e0213397

    • DOI

      10.1371/journal.pone.0213397

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Different Efflux Transporter Affinity and Metabolism of 99mTc-2-Methoxyisobutylisonitrile and 99mTc-Tetrofosmin for Multidrug Resistance Monitoring in Cancer2018

    • Author(s)
      Kobayashi M, Tsujiuchi T, Okui Y, Mizutani A, Nishi K, Nakanishi T, Nishii R, Fukuchi K, Tamai I, Kawai K
    • Journal Title

      Pharm Res

      Volume: 36 Issue: 1 Pages: 18-18

    • DOI

      10.1007/s11095-018-2548-5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differential Diagnosis between Low-Grade and High-Grade Astrocytoma Using System A Amino Acid Transport PET Imaging with C-11-MeAIB: A Comparison Study with C-11-Methionine PET Imaging2018

    • Author(s)
      Nishii Ryuichi、Higashi Tatsuya、Kagawa Shinya、Arimoto Maya、Kishibe Yoshihiko、Takahashi Masaaki、Yamada Shigeki、Saiki Masaaki、Arakawa Yoshiki、Yamauchi Hiroshi、Okuyama Chio、Hojo Masato、Munemitsu Toshihiro、Sawada Masahiro、Kobayashi Masato、Kawai Keiichi、Nagamachi Shigeki、Hirai Toshinori、Miyamoto Susumu
    • Journal Title

      Contrast Media & Molecular Imaging

      Volume: 2018 Pages: 1-9

    • DOI

      10.1155/2018/1292746

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantitative Metabolic Imaging to Detect Hepatic Carboxylesterase Drug-Metabolizing Enzyme Activity Using 123I-Iomazenil.2018

    • Author(s)
      Mizutani A., Kobayashi M., Fujita K., Takahashi K., Hokama T., Takatsu H., Nishi K., Shikano N., Fukuchi K., Kawai K.
    • Journal Title

      Nucl. Med. Commun.

      Volume: 39 Issue: 9 Pages: 825-833

    • DOI

      10.1097/mnm.0000000000000875

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 18F-FPYBF-2, a new F-18-labelled amyloid imaging PET tracer: first experience in 61 volunteers and 55 patients with dementia2018

    • Author(s)
      Higashi Tatsuya、Nishii Ryuichi、Kagawa Shinya、Kishibe Yoshihiko、Takahashi Masaaki、Okina Tomoko、Suzuki Norio、Hasegawa Hiroshi、Nagahama Yasuhiro、Ishizu Koichi、Oishi Naoya、Kimura Hiroyuki、Watanabe Hiroyuki、Ono Masahiro、Saji Hideo、Yamauchi Hiroshi
    • Journal Title

      Ann Nucl Med

      Volume: 32 Issue: 3 Pages: 206-216

    • DOI

      10.1007/s12149-018-1236-1

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PET probe detecting non-small cell lung cancer susceptible to epidermal growth factor receptor tyrosine kinase inhibitor therapy2018

    • Author(s)
      Akira Makino , Anna Miyazaki , Ayaka Tomoike , Hiroyuki Kimura , Kenji Arimitsu , Masahiko Hirata , Yoshiro Ohmomo , Ryuichi Nishii , Hidehiko Okazawa , Yasushi Kiyono , Masahiro Ono , Hideo Saji
    • Journal Title

      Bioorganic & Medical Chemistry

      Volume: 26 Issue: 8 Pages: 1609-1613

    • DOI

      10.1016/j.bmc.2018.02.007

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of radioiodine labeled acetaminophen for specific, high-contrast imaging of malignant melanoma2018

    • Author(s)
      Wen Jing Zhu , Masato Kobayashi , Kohei Yamada , Kodai Nishi , Kotaro Takahashi , Asuka Mizutani , Ryuichi Nishii , Leo G. Flores II , Naoto Shikano , Munetaka Kunishima , Keiichi Kawai
    • Journal Title

      Nuclear Medicine and Biology

      Volume: 59 Pages: 16-21

    • DOI

      10.1016/j.nucmedbio.2017.12.008

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Relationship between [14C]MeAIB uptake and amino acid transporter family gene expression levels or proliferative activity in a pilot study in human carcinoma cells: Comparison with [3H]methionine uptake.2017

    • Author(s)
      Kagawa S, Nishii R, Higashi T, Yamauchi H, Ogawa E, Okudaira H, Kobayashi M, Yoshimoto M, Shikano N, Kawai K.
    • Journal Title

      Nucl Med Biol.

      Volume: 44 Pages: 8-15

    • DOI

      10.1016/j.nucmedbio.2017.01.008

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 18F-Labeled Pyrido[3,4-d]pyrimidine as an Effective Probe for Imaging of L858R Mutant Epidermal Growth Factor Receptor.2017

    • Author(s)
      Hiroyuki Kimura, Haruka Okuda, Masumi Ishiguro, Kenji Arimitsu, Akira Makino, Ryuichi Nishii, Anna Miyazaki, Yusuke Yagi, Hiroyuki Watanabe, Ikuo Kawasaki, Masahiro Ono, and Hideo Saji
    • Journal Title

      ACS Med Chem Lett.

      Volume: 8 Issue: 4 Pages: 418-422

    • DOI

      10.1021/acsmedchemlett.6b00520

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Differences in accumulation and the transport mechanism of l- and d-methionine in high- and low-grade human glioma cells.2017

    • Author(s)
      Masato Kobayashi , Asuka Mizutani , Kodai Nishi , Syuichi Nakajima , Naoto Shikano , Ryuichi Nishii , Kazuki Fukuchi , Keiichi Kawai
    • Journal Title

      Nucl Med Biol.

      Volume: 44 Pages: 78-82

    • DOI

      10.1016/j.nucmedbio.2016.09.003

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] がんの特性を標的としたがん分子PET画像診断― F-18 FEDAC PETおよび C-11 AIB PET―2017

    • Author(s)
      西井 龍一 , 辻 厚至 , 加藤 孝一 , 河村 和紀 , 張 明栄 , 吉永 恵一郎 , 東 達也
    • Journal Title

      臨床核医学

      Volume: 50 Pages: 2-5

    • Related Report
      2016 Annual Research Report
  • [Journal Article] (11)C-methylaminoisobutyric acid (MeAIB) PET for evaluation of prostate cancer: compared with (18)F-fluorodeoxyglucose PET.2016

    • Author(s)
      Maya K Arimoto , Tatsuya Higashi , Ryuichi Nishii , Shinya Kagawa , Masaaki Takahashi , Yoshihiko Kishibe , Hiroshi Yamauchi , Satoshi Ishitoya , Hiroyuki Oonishi , Yuji Nakamoto , Kaori Togashi
    • Journal Title

      Ann Nucl Med.

      Volume: 30 Issue: 8 Pages: 553-62

    • DOI

      10.1007/s12149-016-1098-3

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed

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Published: 2016-04-21   Modified: 2021-02-19  

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