2006 Fiscal Year Final Research Report Summary
Fundamental Studies on the Development of New Diagnostic Radio Tracers Targeting Angiogenesis Factors
| 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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| Keywords | angiogenesis / angiogenesis factor / thymidine phosphorylase / imaiing tracer / PET / [11C]phogne / [11C]5-FU / tumor |
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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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Research Products
(12 results)
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[Journal Article] Synthesis and evaluation of radioiodinated cyclooxygenase-2 inhibitors as potential SPECT tracers for cyclooxygenas-2 expression2006
Author(s)
Y.Kuge, Y.Katada, S.Shimonaka, T.Temma, H.Kimura, Y.Kiyono, C.Yokota, K.Minematsu, Koh-ichi Seki, N.Tamaki, K.Ohkur, H.Saji
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Journal Title
Nuclear Medicine and Biology 3
Pages: 21-27
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Synthesis and evaluation of radioiodinated cyclooxygenase-2 inhibitors as potential SPECT tracers for cyclooxygenas-2 expression2006
Author(s)
Yuji Kuge, Yumiko Katada, Sayaka Shimonaka, Takashi Temma, Hiroyuki Kimura, Yasushi Kiyono, Chiaki Yokota, Kazuo Minematsu4, Koh-ichi Seki5, Nagara Tamaki6, Kazue Ohkura7, Hideo Saji
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Journal Title
Nuclear Medicine and Biology 3 (1)
Pages: 21-27
Description
「研究成果報告書概要(欧文)」より
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