Establishment of Nuclear Medicine Diagnostic Method to Evaluate Drug Metabolizing Enzyme Activity for Personalized Pharmacotherapy Optimization
| Project/Area Number |
18K19508
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 52:General internal medicine and related fields
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
間賀田 泰寛 浜松医科大学, 光尖端医学教育研究センター, 教授 (20209399)
石田 康 宮崎大学, 医学部, 教授 (20212897)
国嶋 崇隆 金沢大学, 薬学系, 教授 (10214975)
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| Project Period (FY) |
2018-06-29 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 薬物代謝酵素 / 個体差要因 / 個別化薬物療法 / 代謝酵素活性 / 核医学画像診断 / 放射性画像診断薬 / cytochrome P450 / 胆汁排泄 / 個別化適正使用 / 代謝酵素活性測定 / 薬物療法 / 薬効・副作用の個体差要因 / 汎用的基盤形成 / 薬物代謝酵素活性 / 核医学画像診断法 |
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| Outline of Final Research Achievements |
Focusing on cytochrome P450 (CYP) as an individual difference factor of drug efficacy and side effects common to drug therapy for psychiatric disorders, we are developing a new radiopharmaceutical suitable for measuring CYP2D6 activity involved in the metabolism of many psychotropic drugs. The antihistamine mequitazine, which is a substrate for CYP2D6, was selected as the labeled parent compound, and the metabolic kinetics of the radioiodine-labeled mequitazine (IMQ) in which the p-iodobenzyl group was introduced into the quinuclidine ring was evaluated. As a result, IMQ showed excellent kinetics satisfying the conditions for drug-metabolizing enzyme activity diagnosis, and thus it has been shown usefulness as a novel drug-metabolizing enzyme activity diagnostic agent capable of quantitatively analyzing drug-metabolizing enzyme activity from the time-activity curve of excretory tissue.
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| Academic Significance and Societal Importance of the Research Achievements |
個体差の大きい精神神経疾患に対する薬物療法の治療効果や副作用発現を予測できる画像診断法を確立することは、薬物療法の個別化の汎用的基盤形成に重要である。本研究では、個人差の大きい個体差要因であり医薬品の個別化適正使用の根拠となる薬物代謝酵素活性の診断法確立と臨床応用を目的として、非侵襲的な分子イメージング法により、多くの医薬品に共通する薬物代謝酵素活性を個別に定量的に測定し得る薬物代謝酵素活性核医学画像診断法の可能性を初めて示した。本研究成果は、個体差の大きい医薬品の適正な投与設計や副作用回避等の個別化薬物療法を最適化する汎用的基盤形成に寄与する点で学術的／社会的意義は大きい。
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Report
(4 results)
Research Products
(30 results)
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[Journal Article] Assessment of drug transporters involved in the urinary secretion of [99mTc]dimercaptosuccinic acid.2021
Author(s)
Kobayashi M, Mizutani A, Okamoto T, Muranaka Y, Nishi K, Nishii R, Shikano N, Nakanishi T, Tamai I, Kleinerman ES, Kawai K.
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Journal Title
Nuclear Medicine and Biology
Volume: 94-95
Pages: 92-97
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Implications for the Use of 6-Radioiodinated L-meta-tyrosine as a Tumor Imaging Agent: Mouse Biodistribution, Renal Autoradiography, and Colon Cancer DLD-1 Cell Studies.2019
Author(s)
Shikano N., Yagi N., Nishii R., Nakajima S., Ogura M., Ikeda A., Kobayashi M., Yamaguchi N., Kawai K.
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Journal Title
ASVPI
Volume: 24
Pages: 13-21
NAID
Related Report
Peer Reviewed
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[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
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Journal Title
Nuclear Medicine and Biology
Volume: 59
Pages: 16-21
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Book] 新核医学技術総論・臨床編2020
Author(s)
日本核医学技術学会編 川井恵一 他64名共著
Total Pages
630
Publisher
山代印刷
ISBN
9784991020131
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