Basic Studies on Biochemical and Molecular Biological Diagnosis of Tumor Hypoxia by PET
| Project/Area Number |
17591260
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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 | National Institute of Radiological Sciences (2006-2007)
University of Fukui (2005) |
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Principal Investigator |
FURUKAWA Takako National Institute of Radiological Sciences, Molecular Imaging Center, Leaser of Molecular Diagnosis Team, Leaser of Molecular Diagnosis Team (00221557)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIBAYASHI Yasuhisa University of Fukui, Biomedical Imaging Center, Professor (50165411)
NAIKI Hironobu University of Fukui, Department of Medicine, 教授 (10227704)
FUJIEDA Shigeharu University of Fukui, Department of Medicine, 教授 (30238539)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | cancer / cell / tissue / hypoxia / PET / acetate / 腫瘍 |
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| Research Abstract |
Noninvasive imaging of tumor hypoxia would be a great help to predict therapy outcome and make treatment planning. Cu-diacetyl-bis (N4-methylthiosemicarbazone) (Cu-ATSM) labeled with positron-emitting Cu is a PET imaging agent which is reduced and trapped in cells under hypoxia. We examined the characteristics of high ^<64>Cu-ATSM uptake regions in mouse tumor mass formed by transplantation of several mouse tumor cells of different tissue origin. The high Cu-ATSM accumulation regions were hypovascular and consisted of tumor cells arrested in the cell cycle, with a few apoptotic cells. In contrast, the regions with high FDG accumulation were well vascularized and consisted of actively proliferating cells as well as highly hypoxic cells and dying cells from necrosis. The region of high Cu-ATSM accumulation seemed to be resistant to radiation and chemotherapy because of hypoxia and lack of vessels compared to high FDG regions where vessels are abundant and cells are proliferating. Cu-ATSM could be useful for therapy planning. It was intriguing that tumor mass contains regions with such unique characteristics in substantial volume. ^<64>Cu-ATSM, which can delineate hypoxic and cell cycle-arrested regions, may provide valuable information for cancer treatment.
As for the production of Cu-64 by clinical small cyclotron and preparation of Cu-ATSM, we have successfully automated the process from the purification of Cu-64 from the target disc after bomberment to preparation of Cu-64 glycine solution, which established safe and reproducible supply of Cu-64 Cu-ATSM.
Studying the characteristics of tumor cell metabolism, we found that acetate metabolism mediated by Acss2 in tumor cells was higher than in normal cells, and the metabolism was increased under hypoxia. These findings suggest a possibility that ^<11>C-acetate PET is visualizing hypoxic up-regulation of acetate metabolism in tumor cells.
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Report
(4 results)
Research Products
(14 results)
