2007 Fiscal Year Final Research Report Summary
Development of PET radiopharmaceuticals for pyrimidine'nucleotide metabolic imaging
| Project/Area Number |
17591288
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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 | Health Sciences University of Hokkaido |
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Principal Investigator |
OHKURA Kazue Health Sciences University of Hokkaido, Pharmaceutical Sciences, Professor (60094827)
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| Co-Investigator(Kenkyū-buntansha) |
TAMAKI Nagara Hokkaido University, Medical Sciences, Professor (30171888)
SEKI Koh-ichi Hokkaido University, Medical Sciences, Professor (60094835)
NISHIJIMA Kenichi Health Sciences University of Hokkaido, Pharmaceutical Sciences, Instructor (60364254)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Nucleic acid / Radiopharmaceuticals / PET / Nuclear medicine / Tumor |
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| Research Abstract |
Uracil derivatives are of considerable interest because of their wide array of pharmacological properties, and many pyrimidine-based radiopharmaceuticals have been developed for clinical diagnosis in the field of single photon or positron emission computed tomography. The search for new or improved synthetic routes leading to labeled thymidine for evaluation of cellular proliferation by PET has attracted much attention in recent years. Recently we have developed a simplified and highly efficient synthesis of [^<11>C]COCl_2 with high specific activity. ^<11>C-Labeled phosgene is a high-potency agent for the introduction of a ^<11>C carbonyl group to form versatile heterocyclic compounds as well as a variety of ureas.
We have demonstrated a novel, efficient synthesis of [2-^<11>C]pyrimidine derivatives including [2-^<11>C]thymine and [2-^<11>C]5-FU, through an analogous method, involving cyclocondentaion of phosogene and the key intermediate □-benzoylamino-□-substituted acrylamides that w
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ould serve as a tumor targeting PET tracer. Because the method involves a simple, mild and rapid procedure, and the yields are essentially good, the present work would provide a general and useful synthesis of various pyrimidine derivatives.
The expression of thymidine phosphorylase (TP) is closely associated with angiogenesis in tumors. For developing a TP-expression-based PET radiotracer for diagnosis and prognosis of cancer chemotherapy, we synthesized a novel ^<11>C-labeled oxoimidazolidinylmethyluracil, which was designed on the basis of one of the most potent inhibitors, 5-bromo-6-[(2-iminoimidazolidinyl)methyl]uracil hydrobromide (5BIMU), through a ring closure reaction of [^(11) C]phosgene with a developed diamine precursor. After purification by HPLC, the total synthesis was accomplished in just 23 min after bombardment, and the yield was 1653 MBq at the end of synthesis. The new radiotracer can be used as a PET radiopharmaceutical for imaging angiogenic enzyme TP expression due to its TP inhibitory potency. Less
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[Journal Article] Synthesis and evaluation of radioiodinated cyclooxygenase-2 inhibit ors 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, K.Seki, N.Tamaki, K.Ohkura H.Saji
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Journal Title
Nuclear Medicine and Biology 33
Pages: 21-27
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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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, K. Seki, N. Tamaki, K. Ohkura, H. Saji
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Journal Title
Nuclear Medicine and Biology 33
Pages: 21-27
Description
「研究成果報告書概要(欧文)」より
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