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Measurement of intracerebral drug concentration using magnetic resonance spectroscopy (MRS)

Research Project

Project/Area Number 16H05385
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionTohoku University

Principal Investigator

TASHIRO Manabu  東北大学, サイクロトロン・ラジオアイソトープセンター, 教授 (00333477)

Co-Investigator(Kenkyū-buntansha) 久保 均  福島県立医科大学, 新医療系学部設置準備室, 教授 (00325292)
伊藤 浩  福島県立医科大学, 医学部放射線科, 教授 (20360357)
渡部 浩司  東北大学, サイクロトロン・ラジオアイソトープセンター, 教授 (40280820)
佐々木 真理  岩手医科大学, 医歯薬総合研究所, 教授 (80205864)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Keywords核磁気共鳴スペクトロスコピー(MRS) / ポジトロン放出断層法(PET) / 脳・神経 / 薬理学 / 脳内代謝物 / MRS / PET / 薬物動態 / 脳 / 薬物血中濃度 / 薬物脳内濃度 / 薬物代謝物濃度 / ポジトロン放出断層法(PET) / 受容体占拠率 / 脳内代謝物濃度
Outline of Final Research Achievements

In this project, non-invasive measurement of the intra-cerebral concentrations of orally-administered drugs (e.g. acetoaminophen or diphenhydramine) was tested in healthy humans using MR spectroscopy (MRS) function of PET/MR system. Results suggested it was not yet applicable to the measurement of other drugs although previous studies succeeded in measuring intra-cerebral ethanol concentration in humans. However, the results also demonstrated correlations between the plasma concentration change of the orally-administered drugs and intra-cerebral concentration of some selected brain metabolites. Based on this finding, it might be possible to estimate the intra-cerebral concentrations of orally-administered drugs in future.
In addition, additional PET measurement demonstrated an increased cerebral glucose consumption following oral administration of diphenhydramine especially during cognitive tasks. This finding might be useful to evaluate the effects of drugs on human brain activity.

Academic Significance and Societal Importance of the Research Achievements

本研究では、ヒトが内服した薬物のうち脳内に分布した薬物分子に由来するMRS信号を体外計測して薬物の脳内濃度を推定することを目指したが、現在のMRS技術では困難であると示された。一方、服薬後の脳内代謝物由来のMRS信号を利用して内服薬物の脳内濃度を推定できる可能性があることが示唆され、将来、他の薬剤を用いた測定の実施が期待される。また、将来的にMRSの測定感度とデータ処理技術がさらに進歩した際には、ヒトの脳内薬物濃度を体外測定できる可能性があると期待される。
加えて、PETによる付随所見である薬物内服後の認知課題負荷時の脳代謝増加所見は、薬物による脳への影響を評価する指標としても有用と考えられた。

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

    (39 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (4 results) Journal Article (16 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 16 results,  Open Access: 9 results) Presentation (19 results) (of which Int'l Joint Research: 5 results,  Invited: 9 results)

  • [Int'l Joint Research] Charite - Universitaetsmedizin Berlin(ドイツ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Charite - Universitaetsmedizin Berlin(ドイツ)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Charite - Universitaetsmedizin Berlin(ドイツ)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Charite - Universitaetsmedizin Berlin(ドイツ)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Alzheimer's deterioration in intellectual and neurobiological staging supports the retrogenesis model: a double dissociation between verbal/non-verbal judgments and the left/right parieto-temporal glucose metabolism. A retrospective data analysis from the Tajiri Project.2020

    • Author(s)
      Meguro M, Meguro K, Takahashi K, Yamaguchi S, Tashiro M.
    • Journal Title

      Psychogeriatrics.

      Volume: 20 Issue: 2 Pages: 149-155

    • DOI

      10.1111/psyg.12478

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A systematic performance evaluation of head motion correction techniques for 3 commercial PET scanners using a reproducible experimental acquisition protocol2019

    • Author(s)
      Takato Inomata,Shoichi Watanuki,Hayato Odagiri,Takeyuki Nambu,Nicolas A. Karakatsanis,Hiroshi Ito,Hiroshi Watabe,Manabu Tashiro,Miho Shidahara
    • Journal Title

      Annals of Nuclear Medicine

      Volume: - Issue: 7 Pages: 459-470

    • DOI

      10.1007/s12149-019-01353-w

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Longitudinal changes in 18F-THK5351 PET in corticobasal syndrome2019

    • Author(s)
      Ezura M, Kikuchi A, Ishiki A, Okamura N, Hasegawa T, Harada R, Watanuki S, Funaki Y, Hiraoka K, Baba T, Sugeno N, Oshima R, Yoshida S, Kobayashi J, Kobayashi M, Tano O, Nakashima I, Mugikura S, Iwata R, Taki Y, Furukawa K, Arai H, Furumoto S, Tashiro M, Yanai K, Kudo Y, Takeda A, Aoki M
    • Journal Title

      Eur J Neurol

      Volume: 26 Issue: 9 Pages: 1205-1211

    • DOI

      10.1111/ene.13966

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nuclear medicine practice in Japan: a report of the eighth nationwide survey in 2017.2019

    • Author(s)
      Nishiyama Y, Kinuya S, Kato T, Kayano D, Sato S, Tashiro M, Tatsumi M, Hashimoto T, Baba S, Hirata K, Yoshimura M, Yoneyama H.
    • Journal Title

      Ann Nucl Med.

      Volume: 33 Issue: 10 Pages: 725-732

    • DOI

      10.1007/s12149-019-01382-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Brain histamine H1 receptor occupancy after oral administration of desloratadine and loratadine2019

    • Author(s)
      Nakamura Tadaho、Hiraoka Kotaro、Harada Ryuichi、Matsuzawa Takuro、Ishikawa Yoichi、Funaki Yoshihito、Yoshikawa Takeo、Tashiro Manabu、Yanai Kazuhiko、Okamura Nobuyuki
    • Journal Title

      Pharmacology Research & Perspectives

      Volume: 7 Issue: 4

    • DOI

      10.1002/prp2.499

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Error evaluation of the D-shuttle dosimeter technique in positron emission tomography study.2019

    • Author(s)
      Islam MS, Watanuki S, Tashiro M, Watabe H.
    • Journal Title

      Radiol Phys Technol.

      Volume: 12 Issue: 4 Pages: 363-373

    • DOI

      10.1007/s12194-019-00530-w

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Renal statistical map for positron emission tomography with [O-15] water.2019

    • Author(s)
      Rahman M, Watabe H, Shidahara M, Watanuki S, Tashiro M, Mori T, Ito S, Ohsaki Y.
    • Journal Title

      Am J Nucl Med Mol Imaging.

      Volume: 9 Pages: 193-202

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Investigation of the quantitative accuracy of low-dose amyloid and tau PET imaging.2018

    • Author(s)
      Nai YH, Watanuki S, Tashiro M, Okamura N, Watabe H.
    • Journal Title

      Radiol Phys Technol.

      Volume: 11 Issue: 4 Pages: 451-459

    • DOI

      10.1007/s12194-018-0485-y

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Internal radiation dose estimation using multiple D-shuttle dosimeters for positron emission tomography (PET): A validation study using NEMA body phantom.2018

    • Author(s)
      Islam MS, Watanuki S, Tashiro M, Watabe H.
    • Journal Title

      Med Phys.

      Volume: 45 Issue: 10 Pages: 4693-4703

    • DOI

      10.1002/mp.13124

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Relationship between sympathoadrenal and pituitary-adrenal response during colorectal distention in the presence of corticotropin-releasing hormone in patients with irritable bowel syndrome and healthy controls.2018

    • Author(s)
      Tanaka Y, Kanazawa M, Kano M, Tashiro M, Fukudo S.
    • Journal Title

      PLoS One

      Volume: 13 Issue: 7 Pages: 1-16

    • DOI

      10.1371/journal.pone.0199698

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuroimaging-pathological correlations of [(18)F]THK5351 PET in progressive supranuclear palsy2018

    • Author(s)
      Ishiki A, Furukawa K, et al.
    • Journal Title

      Acta Neuropathol Commun

      Volume: 6 Issue: 1 Pages: 53-53

    • DOI

      10.1186/s40478-018-0556-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Newly-Developed Positron Emission Mammography (PEM) Device for the Detection of Small Breast Cancer2018

    • Author(s)
      Yanai A, Itoh M, Hirakawa H, Yanai K, Tashiro M, Harada R, Yoshikawa A, Yamamoto S, Ohuchi N, Ishida T.
    • Journal Title

      The Tohoku Journal of Experimental Medicine

      Volume: 245 Issue: 1 Pages: 13-19

    • DOI

      10.1620/tjem.245.13

    • NAID

      130006731329

    • ISSN
      0040-8727, 1349-3329
    • Related Report
      2018 Annual Research Report 2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of levocetirizine and diphenhydramine on regional glucose metabolic changes and hemodynamic responses in the human prefrontal cortex during cognitive tasks.2018

    • Author(s)
      Kikuchi A, Nasir FBM, Inami A, Mohsen A, Watanuki S, Miyake M, Takeda K, Koike D, Ito T, Sasakawa J, Matsuda R, Hiraoka K, Maurer M, Yanai1 K, Watabe H, Tashiro M.
    • Journal Title

      Human Psychopharmacology.

      Volume: 33 Issue: 2

    • DOI

      10.1002/hup.2655

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Correlations of (18)F-THK5351 PET with Postmortem Burden of Tau and Astrogliosis in Alzheimer Disease.2018

    • Author(s)
      Harada R, Furukawa K, et al.
    • Journal Title

      J Nucl Med

      Volume: 59 Issue: 4 Pages: 671-674

    • DOI

      10.2967/jnumed.117.197426

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A comparison of five partial volume correction methods for Tau and Amyloid PET imaging with [(18)F]THK5351 and [(11)C]PIB.2018

    • Author(s)
      Shidahara M, Thomas BA, Okamura N, Ibaraki M, Matsubara K, Oyama S, Ishikawa Y, Watanuki S, Iwata R, Furumoto S, Tashiro M, Yanai K, Gonda K, Watabe H.
    • Journal Title

      Ann Nucl Med.

      Volume: 59 Issue: 7 Pages: 671-674

    • DOI

      10.1007/s12149-017-1185-0

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The clinical pharmacology of non-sedating antihistamines.2017

    • Author(s)
      Yanai K, Yoshikawa T, Yanai A, Nakamura T, Iida T, Leurs R, Tashiro M.
    • Journal Title

      Pharmacol Ther.

      Volume: 178 Pages: 148-156

    • DOI

      10.1016/j.pharmthera.2017.04.004

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 抗ヒスタミン薬の鎮静作用と自動車運転における安全性:脳科学からの考察2020

    • Author(s)
      田代学
    • Organizer
      遠野市医師会学術講演会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 抗ヒスタミン薬が認知課題遂行中のエネルギー消費に与える影響:FDG-PET研究.2019

    • Author(s)
      田代 学、鈴木 頌也、Edmond CHEN、菊地 飛鳥 、稲見 暁惠、三宅 正泰、Fairuz Mohd NASIR、平岡 宏太良、四月朔日聖一、谷内 一彦、渡部 浩司.
    • Organizer
      第59回日本核医学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脳画像医学で明らかにされる抗ヒスタミン薬の鎮静性副作用:ガンマ線および近赤外線を用いた脳イメージング技術の医学貢献.2019

    • Author(s)
      田代学.
    • Organizer
      第41回日本光医学光生物学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Effects of antihistamines on regional glucose metabolic changes in human prefrontal cortex during cognitive tasks2019

    • Author(s)
      Nobuya Suzuki, Asuka Kikuchi, Akie Inami, Fairuz Binti Mohammadi Nasir, Attayeb Mohsen, Shoichi Watanuki, Masayasu Miyake, Kazuko Takeda, Kotaro Hiraoka, Kazuhiko Yanai, Hiroshi Watabe, Manabu Tashiro.
    • Organizer
      NEURO2019(第42回日本神経科学大会)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 一過性の運動による認知パフォーマンスの向上に対する内因性ドーパミンの関与.2019

    • Author(s)
      安藤創一,藤本敏彦,四月朔日聖一,Fairuz Nasirナジールファイルーズ,平岡宏太良,武田和子,小林中,今野大成,リンユーチェンYuchen Lin,渡部浩司,田代学.
    • Organizer
      第74回体力医学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 抗ヒスタミン薬が認知課題遂行中の脳エネルギー消費に与える影響に関する脳PET研究2019

    • Author(s)
      鈴木頌也、菊地飛鳥、稲見暁惠、Attayeb Mohsen、松田林、平岡宏太良、四月朔日聖一、三宅正泰、渡部浩司、谷内一彦、田代学
    • Organizer
      第22回日本ヒスタミン学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Application of Nuclear Medicine to Brain research2019

    • Author(s)
      Tashiro M.
    • Organizer
      Advanced Medical Imaging Physics: Egypt-Japan
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Status of Nuclear Medicine in Japan2019

    • Author(s)
      Tashiro M.
    • Organizer
      Advanced Medical Imaging Physics: Egypt-Japan
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Functional Neuro-Imaging Research on Dementia2019

    • Author(s)
      Tashiro M.
    • Organizer
      17th Annual Meeting of Egyptian Society of Nuclear Medicine Specialists
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Evaluation of Double Injection Method for FDG PET Brain study2018

    • Author(s)
      Edmond Chen, Asuka Kikuchi, Akie Inami, Fairuz Binti Mohd Nasir, Attayeb Mohsen, Shoichi Watanuki, Masayasu Miyake, Kazuko Takeda, Kotaro Hiraoka, Kazuhiko Yanai, Hiroshi Watabe, Manabu Tashiro
    • Organizer
      日本ヒト脳機能イメージング研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The recognition of small skeletal muscles: Pilot studies using PET/CT, PEM and PET/MR with 18F-FDG2018

    • Author(s)
      Yu-Chen Lin, Fumihiko Sato, Xudong Duan, Hitoshi Kubo, Taisei Konno, Katsuhiko Shibuya, Toshie Sugai, Ayaka Nemoto, Chieh-Hsiang Hsu, Soichi Ando, Hiroshi Itoh, Li-Chieh Kuo, Masatoshi Itoh, Manabu Tashiro
    • Organizer
      日本核医学会北日本地方会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Effects of antihistamines on regional cerebral glucose metabolism and perfusion during cognitive tasks2018

    • Author(s)
      Asuka Kikuchi, Manabu Tashiro, Akie Inami, Fairuz Binti Mohammadi Nasir, Attayeb Mohsen, Shoichi Watanuki, Masayasu Miyake, Yuma Arakawa, Kazuko Takeda, Daigo Koike, Takayasu Ito, Junpei Sasakawa, Rin Matsuda, Kotaro Hiraoka, Kazuhiko Yanai, Hiroshi Watabe
    • Organizer
      World Histamine Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脳科学が語る抗ヒスタミン薬の鎮静性副作用2018

    • Author(s)
      田代学
    • Organizer
      柴田郡医師会学術講演会
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Invited
  • [Presentation] 脳科学が語る抗ヒスタミン薬の鎮静性副作用2018

    • Author(s)
      田代学
    • Organizer
      TAIHO Web Lecture for Allergy
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Invited
  • [Presentation] Effects of antihistamines on regional cerebral glucose metabolism and perfusion during cognitive tasks.2018

    • Author(s)
      Kikuchi A, Tashiro M, Inami A, Fairuz BMN, Attayeb M, Watanuki S, Miyake S, Arakawa Y, Takeda K, Koike D, Ito T, Sasakawa J, Matsuda R, Hiraoka K, Yanai K, Watabe H.
    • Organizer
      Asia Oceania Congress of Nuclear Medicine and Biology
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] FDG-double-injection法による残留放射能補正の検討.2018

    • Author(s)
      菊地飛鳥、田代学、渡部浩司、四月朔日聖一
    • Organizer
      第37回日本核医学技術学会学術総会
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
  • [Presentation] レボセチリジンの鎮静作用に関する脳ブドウ糖代謝および脳血流の変化の観察2018

    • Author(s)
      田代学、菊地飛鳥、稲見暁惠、三宅正泰、Attayeb Mohsen、Fairuz Mohd Nasir、松田林、平岡宏太良、四月朔日聖一、谷内一彦、渡部浩司
    • Organizer
      第38回日本臨床薬理学会学術総会
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
  • [Presentation] 脳科学が語る抗ヒスタミン薬の鎮静性副作用.2017

    • Author(s)
      田代学
    • Organizer
      阪神アレルギーシンポジウム
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Invited
  • [Presentation] 脳科学が語る抗ヒスタミン薬の鎮静性副作用: 眠気とインペアードパフォーマンス2017

    • Author(s)
      田代学
    • Organizer
      Taiho Allergy Conference in Okinawa
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Invited

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

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