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Prediction and evaluation of therapeutic effect of melphalan, a first-line drug for multiple myeloma: Development of PET imaging method

Research Project

Project/Area Number 15K09954
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Radiation science
Research InstitutionOsaka Medical College (2018)
Osaka University (2015-2017)

Principal Investigator

Isohashi Kayako  大阪医科大学, 医学部, 助教 (50598604)

Co-Investigator(Kenkyū-buntansha) 畑澤 順  大阪大学, 医学系研究科, 教授 (70198745)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsPET-CT / 多発性骨髄腫 / MET / FDG / FBPA / 悪性腫瘍 / MRI / 治療効果 / 代謝 / PET/CT
Outline of Final Research Achievements

Melphalan, a therapeutic agent for multiple myeloma (MM), acts via the tumor cell membrane neutral amino acid transporter (LAT1). If LAT1 expression could be predicted, it would be possible to predict the therapeutic effect. Cell-transplanted small animal tumor models of MM and malignant lymphoma (ML) were created. PET was performed using methionine (MET) and FBPA with high LAT1 affinity and compared to FDG PET. High expression of LAT1 in MM and ML cells was confirmed by flow cytometry. The MM model showed no difference in the uptake of MET, FDG and FBPA, and the ML model showed weak MET, but no difference in the uptake of FDG and FBPA. High LAT1 expression was thought to be related to the uptake of FBPA.

Academic Significance and Societal Importance of the Research Achievements

本研究では、多発性骨髄腫(MM)並びに悪性リンパ腫(ML)の腫瘍細胞移植小動物モデルを用いたPET-CT評価を行い、腫瘍細胞のLAT1高発現はアミノ酸トレーサの一つであるFBPAの取り込みと関係があることが示唆された。健常成人におけるmethionine(MET)の生理的集積は肝臓や膵臓で強く、FDGの生理的集積は脳や尿路排泄経路で強い。それに対して、FBPAの生理的集積は尿路排泄経路を除いて各臓器で全体に低く、臨床応用が期待できると考えられた。今後、臨床研究が開始できるように倫理委員会への書類準備並びに申請、薬剤合成の準備などをすすめていく。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (15 results)

All 2018 2017 2016 2015

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (12 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results)

  • [Journal Article] Preliminary feasibility study on differential diagnosis between radiation-induced cerebral necrosis and recurrent brain tumor by means of [18F]fluoro-borono-phenylalanine PET/CT.2018

    • Author(s)
      Beshr R, Isohashi K, Watabe T, Naka S, Horitsugi G, Romanov V, Kato H, Miyatake SI, Shimosegawa E, Hatazawa J.
    • Journal Title

      Ann Nucl Med

      Volume: 32 Pages: 702-708

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparison of the image-derived radioactivity and blood-sample radioactivity for estimating the clinical indicators of the efficacy of boron neutron capture therapy (BNCT): 4-borono-2-18F-fluoro-phenylalanine (FBPA) PET study.2016

    • Author(s)
      Isohashi K, et al.
    • Journal Title

      EJNMMI Res.

      Volume: 6 Pages: 75-75

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Prognostic Value of FDG-PET, Based on the Revised Response Criteria, in Patients with Malignant Lymphoma: A Comparison with CT/MRI Evaluations, Based on the International Working Group/ Cotswolds Meeting Criteria.2015

    • Author(s)
      Isohashi K, et al.
    • Journal Title

      AOJNMB

      Volume: 3 Pages: 91-98

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Estimation of boron (10B) concentration in blood and target tumors after therapeutic dose administration of borono-phenylalanine (BPA) using FBPA PET in boron neutron capture therapy2018

    • Author(s)
      Kayako Isohashi, Sadahiro Naka, Yasukazu Kanai, Genki Horitsugi, Tadashi Watabe, Hiroki Kato, Mitsuaki Tatsumi, Eku Shimosegawa, Jun Hatazawa
    • Organizer
      Society of Nuclear Medicine and Molecular Imaging's 64th Annual Meeting(SNMMI2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脳腫瘍患者におけるFBPA PET/CTを用いたホウ素濃度の推定2018

    • Author(s)
      礒橋佳也子、小野公二、金井泰和、小森剛、鳴海善文、畑澤順
    • Organizer
      第15回日本中性子補足療法学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Estimation of boron concentration in blood and tumor using FBPA PET in BNCT2018

    • Author(s)
      Kayako Isohashi, Yasukazu Kanai, Tsuyoshi Komori, Yoshifumi Narumi, Koji Ono, Jun Hatazawa
    • Organizer
      第58回日本核医学学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Selection criteria for boron neutron capture therapy candidates based on the SUV images of FBPA PET.2017

    • Author(s)
      Isohashi K, Kato H, Tatsumi M, Naka S, Kanai Y, Horitsugi G, Watabe T, Shimosegawa E, Hatazawa J.
    • Organizer
      Society of Nuclear Medicine and Molecular Imaging's 63th Annual Meeting(SNMMI 2017).
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] ホウ素中性子捕捉療法とFBPA-PET2017

    • Author(s)
      礒橋佳也子
    • Organizer
      第17回日本核医学会春季大会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] BNCTにおけるFBPA-PETの役割について2017

    • Author(s)
      礒橋佳也子
    • Organizer
      第2回 Advanced Medical Imaging 研究会(SAMI 2017)
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Estimation of Boron Concentration in Tumors and Surrounding Tissues in Brain Tumor Patients Using FBPA PET.2017

    • Author(s)
      Isohashi K, Kato H, Naka S, Kanai Y, Horitsugi G, Kamiya T, Matsunaga K, Watabe T, Tatsumi M, Shimosegawa E, Hatazawa J.
    • Organizer
      第57回日本核医学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 4-borono-2-18F-fluoro-phenylalanine (FBPA) PET-CT evaluation in tumor patients before boron neutron capture therapy (BNCT).2016

    • Author(s)
      Isohashi K, et al.
    • Organizer
      2016 日本核医学学会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2016-11-03
    • Related Report
      2016 Research-status Report
  • [Presentation] 腫瘍患者におけるFBPA PET/CT評価2016

    • Author(s)
      礒橋佳也子等
    • Organizer
      2016 中性子補足療法学会
    • Place of Presentation
      東京大学
    • Year and Date
      2016-08-06
    • Related Report
      2016 Research-status Report
  • [Presentation] Early treatment effects with anti-CD20 immunotherapy in aggressive non-Hodgkin lymphoma: Histopathological, MR-based morphometric, and FDG PET/CT-based metabolic studies in nude rats.2016

    • Author(s)
      Isohashi K, et al.
    • Organizer
      SNMMI 2016
    • Place of Presentation
      San Diego Convention Center, America
    • Year and Date
      2016-06-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Dynamic whole body distribution of FBPA in humans studied with 3D PET/CT2015

    • Author(s)
      Isohashi K,et al.
    • Organizer
      Annual Congress of the European Association of Nuclear Medicine (EANM’15)
    • Place of Presentation
      Hamburg, Germany
    • Year and Date
      2015-10-10
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Comparison of the T / B ratio in healthy volunteers and tumor patients.2015

    • Author(s)
      Isohashi K,et al.
    • Organizer
      第12回日本中性子補足療法学会学術大会
    • Place of Presentation
      神戸学院大学
    • Year and Date
      2015-09-04
    • Related Report
      2015 Research-status Report
    • Invited

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Published: 2015-04-16   Modified: 2020-03-30  

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