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癌治療、診断用新規放射性医薬品の創薬:機能性有機金属錯体の合成と代謝生理学的研究

Research Project

Project/Area Number 12771423
Research Category

Grant-in-Aid for Encouragement of Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

榎本 秀一  理化学研究所, ラジオアイソトープ技術室, 先任研究員 (10271553)

Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywordsマルチトレーサー / RI標識モノクローナル抗体 / 臓器分布 / 腫瘍蓄積性 / 亜鉛 / バナジウム錯体 / マンガン / 代謝過程 / DOTA錯体 / リングサイクロトロン
Research Abstract

ラジオアイソトープ(RI)標識モノクローナル抗体に関する技術は、臨床治療が行われ有用性が確かめられたが、臨床には利用できない現状である。
本年度、申請者は、理研リングサイクロトロンで製造したマルチトレーサー法を用いて、Diethlenetriamine-pentaacetic acid (DTPA)を付加したヒト化抗体の各種金属の血清成分との結合特性と担癌マウスを使った生体中での臓器特異性と代謝過程とそのダイナミクスについて明らかにした。また、peptide-DOTAやDOTAフォームを維持したSCN-Bz-DOTAを合成し、生体内動態を担癌マウスを用いて調べた。これらの標識モノクローナル抗体は、腫瘍の萎縮効果を有し、特異的腫瘍濃縮を示し、新規放射性医薬品としての応用の可能性を示唆した。
一方、亜鉛およびマンガンが脳腫瘍に特異的に蓄積することを明らかにした。さらには糖尿病治療薬として利用の可能性がある、バナジウム錯体化合物を投与した糖尿病モデル動物の血糖値降下作用と各種元素の取り込みに対する影響を検討し、新規放射性医薬品の開発のみならず、糖尿病治療薬としての錯化合物の代謝過程に対する前臨床研究にマルチトレーサー法が有効であることを証明できた。これにより、新規の癌治療、診断薬の創薬に向けた知見が得ることを目的とし、研究を推進している。

Report

(2 results)
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Enomoto S. et al.: "Zinc-65 imaging of rat brain tumors"Cancer Research. 61. 5065-5069 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Enomoto S. et al.: "Comparative uptake behavior of trace elements in adult and suckling rat lens"Toxicology. 163. 101-105 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Enomoto S. et al.: "Fetoplacental transport of various trace elements in pregnant rat using the multitracer technique"RIKEN Rev.. 35. 31-34 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Enomoto S. et al.: "Effect of vanadium treatment on tissue distribution of biotrace elements in normal and streptozotocin-induced diabetic rats : Simultaneous analysis of V and Zn using radioactive multitracer"RIKEN Rev.. 35. 45-47 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Enomoto S. et al.: "Distribution of biotrace elements in partially hepatectomized rats"RIKEN Rev.. 35. 48-49 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Enomoto S. et al.: "MT-GEI : A new detection system for multitracer"RIKEN Rev.. 35. 116-117 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Enomoto S. et al.: "Brain regional uptake of radioactive Sc, Mn, Zn, Se, Rb and Zr tracers into normal mice during aging"J.Radioanal. Nucl. Chem.. 247. 507-511 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Enomoto S. et al.: "A compton camera for multitracer imaging"IEEE Trans. Nucl. Sci.. 48. 656-661 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Enomoto S. et al.: "Contents and uptake rates of Mn, Fe, Co, Zn, and Se in Se-deficient rat liver cell fractions"Anal. Sci.. 17. 587-591 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Enomoto S. et al.: "Tumor accumulation of radioactive trace elements : A multitracer study"Biomed. Res. Trace Elements. 12. 311-315 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Enomoto S. et al.: "多元素同時代謝分析法としてのマルチトレーサー法:生体微量元素研究へのアプローチ"Biomed. Res. Trace Elements. 12. 311-315 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Enomoto S. et al.: "Prompt gamma-ray analysis of rats"J.Radioanal. Nucl. Chem.. 244. 311-315 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Enomoto S. et al.: "Hepatic zinc response via metallothionein induction after tumor transplantation"Biochem. Biophys. Res. Commun.. 270. 1140-1143 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Enomoto S. et al.: "バナジウムによる糖尿病の制御"Biomed. Res. Trace Elements. 11. 311-312 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Enomoto S. et al.: "母体-胎盤間における各種微量元素の透過と蓄積性"Biomed. Res. Trace Elements. 11. 439-440 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Enomoto S. et al.: "Trace Elements in Man and Animals 10"Kluwer Academic/Plenum Publishers. 1172 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] 榎本秀一: "サイアス2000/04"朝日新聞社. 130 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Enomoto S. et al.: "Hepatic zinc response via metallothionein induction after tumor transplantation"Biochem.Biophys.Res.Commun.. 270. 1140-1143 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Enomoto S. et al.: "Suppression of a high-affinity transport system for manganese in cadmium-resistant metallothionein-null cells"J.Pharmacol.Exp.Ther.. 292. 1080-1086 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Enomoto S. et al.: "A survey of trace elements in pteridophytes"Biol.Trace Elem.Res.. 74. 259-273 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Enomoto S. et al.: "Beneficial effect of rare earth elements on the growth of Dryopteris erythrosora"J.Plant Physiol.. 156. 330-334 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Enomoto S. et al.: "Uptake of 15 trace elements in arbuscular mycorrhizal marigold measured by the multitracer technique"Soil Sci.Plant Nutr.. 46. 283-289 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Enomoto S. et al.: "Tumor accumulation of radioactive trace elements : a multitracer study"Biomed.Res.Trace Elements. (in press).

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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