103(P-40) 酸素-15標識2-デオキシ-D-グルコースの超高速合成とバイオイメージングへの利用(ポスター発表の部)

• 依光 英樹

  東大院理

• 村上 佳裕

  藤沢薬品工業:先端医学薬学研究センター

• 高松 宏幸

  藤沢薬品工業:先端医学薬学研究センター

• 西村 伸太郎

  藤沢薬品工業:先端医学薬学研究センター

• 中村 栄一

  東大院理

書誌事項

タイトル別名

• 103(P-40) Ultra-rapid Synthesis and Bio-imaging of ^<15>O-Labeled 2-Deoxy-D-glucose

抄録

In positron emission tomography (PET), a systematic repertoire of oxygen-15-labeled PET tracers would be useful owing to the ubiquity of oxygen atoms in organic compounds. Because of the 2-min half-life of ^<15>O, however, no organic compounds more complex than 1-|^<15>O|butanol have been available. The synthesis of an ^<15>O-labeled complex organic molecule being ever possible and practically useful, it must be exceedingly rapid and clean. In the light of the capability of PET to image in vivo glucose metabolism, we have chosen 6-|^<15>O|-2-deoxy-D-glucose (|^<15>O|DG) as our first target to establish the feasibility of the required ultra-rapid organic synthesis, which we report herein. We previously developed a radical oxygenation reaction starting with an alkyl halide, air, Bu_3SnH and a small amount of azobis(isobutyronitrile), and used it for ^<17>O- and ^<18>O-labeling of complex organic molecules. For the ^<15>O-labeling, a number of fundamental problems, however, needed to be resolved: (1) Drastic reduction of the reaction time from over 10 hours in air to a few minutes, fighting against the low-concentration ^<15>O^<16>Ogas supplied, (2) erratic induction time inherent to radical chain reactions, (3) the use of a OH-free sugar substrate to avoid time loss of deprotection, (4) enhancement of the reaction selectivity and (5) a variety of synthetic and operational issues related to radioactivity and automation. To make efficient utilization of the ^<15>O^<16>O gas, we used a CF_3C_6H_5/perfluorodecalin/2-butanol mixture as a solvent. The reactant solution was placed in a reaction vessel equipped with a sintered glass bottom, through which the oxygen gas was introduced as fine bubbles. Purification of the desired labeled sugar employed a solid phase extraction technique. Ultra-rapid radical hydroxylation of 6-iodo-2,6-dideoxy-D-glucose with |^<15>O|O_2 have now made available the ^<15>O-labeled compound, |^<15>O|DG. A saline solution of |^<15>O|DG was prepared and administered to a rat. The distribution of |^<15>O|DG was measured with the aid of a planar positron imaging system. This image is essentially the same as that obtained with 2-deoxy-2-|^<18>F|fluoro-D-glucose (|^<18>|FDG), which reflects the accumulations in the heart, kidneys, and bladder, hence imaging the glucose metabolism in the test animal. We could also perform sequential |^<15>O|DG-|^<15>O|H_2O-|^<18>F|FDG measurement at intervals of five minutes to obtain similar images. The ^<15>O-labeling thus offers repetitive scanning and use of multiple PET tracers in the same body within a short time, and hence will significantly expand the scope of the PET studies.

収録刊行物

• 天然有機化合物討論会講演要旨集

  天然有機化合物討論会講演要旨集 46 (0), 593-598, 2004

  天然有機化合物討論会実行委員会

詳細情報

• CRID: 1390001206078268032
• NII論文ID: 110006682484
• DOI: 10.24496/tennenyuki.46.0_593
• ISSN: 24331856
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可