| Project/Area Number |
16591179
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Hokkaido University |
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Principal Investigator |
SEKI Koh-ichi Hokkaido University, Central Institute of Radio Isotope Science, Professor, アイソトープ総合センター, 教授 (60094835)
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| Co-Investigator(Kenkyū-buntansha) |
TAMAKI Nagara Hokkaido University, Graduate School of Medicine, Professor, 大学院医学研究科, 教授 (30171888)
OHKURA Kazue Health Sciences University of Hokkaido, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (60094827)
NISHIJIMA Kenichi Health Sciences University of Hokkaido, Faculty of Pharmaceutical Sciences, Assistant Professor, 薬学部, 助手 (60364254)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | angiogenesis / angiogenesis factor / thymidine phosphorylase / imaiing tracer / PET / [11C]phogne / [11C]5-FU / tumor / 腫瘍診断薬剤 / 放射性標識薬剤 / Thymidine Phosphorylase / 5-Bromo-6-[2-(oxoimidazolidinyl)methyl]uracil / 細胞増殖能評価薬剤 / 陽電子放出画像診断薬剤 / ^<11>C-ホスゲン / 2-^<11>C-チミジン / β-アミノメタクリルアミド誘導体 |
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| Research Abstract |
Thymidine phosphorylase (TP), an enzyme involved in pyrimidine nucleoside metabolism has been demonstrated to be identical with PD-ECGF, an angiogenetic factor, and is an attractive target for imaging and therapy because of the strong relationship between its expression in tumor biopsies and clinical outcome in many tumor types. Various effective TP inhibitory chemicals consisting of a pyrimidine moiety have been reported.
On the basis of one the most efficient TP inhibitor, 5-Bromo-6-[(2-iminoimidazolidinyl)-methyl] uracil hydrobromide, we have designed [^<11>C]phosgene based [11C] 5-Bromo-6-[2-(oxoimidazolidinyl)methyl]uracil ([^<11>C]-BOMU) as a new diagnostic PET tracers targeting angiogenesis factor.
The key intermediate 6-{[2-(aminoethyl)amino]methyl}-5-bromouracil was readily synthesized from 6-chloromethyluracil through three steps. Condensation of the key intermediate with [^<11>C]-phosgene afforded [^<11>C]-BOMU in high efficiency with specific radio activities.
The synthesized [^<11> CJ-BOMU showed TP inhibitory activity, suggesting the possible PET imaging tracer targeting angiogenesis.
We intended to apply the above the phosgene based condensation reaction to the synthesis of [^<11>C]-5FU. Although [^<11>C]-5FU was recognized as a useful PET-tracer for the assessment and prediction of outcomes of 5-FU in chemotherapeutic treatment, no effective synthetic method has not been developed.
The [^<11>C] COCl_<2> based condensation seemed promising for the efficient synthesis of [2-^<11>C] 5-fluorouracil. The key intermediate (E)-β-benzoylamino-□-fluoroacrylic amid was successfully prepared from p-aminoacrylate. The prepared β-aminoacrylate successfully underwent condensation with [^<11>C]C0Cl_<2> to give [11C]5-FU in high efficiency with high specific radio activities.
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