| Project/Area Number |
09470196
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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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 | Tohoku University |
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Principal Investigator |
FUKUDA Hiroshi Institute of Development, Aging and Cancer, Tohoku University, Dept. of Nuclear Medicine and Radiology, Professor, 加齢医学研究所, 教授 (30125645)
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| Co-Investigator(Kenkyū-buntansha) |
IWATA Ren Graduate School of Engnering, Quantum Science and Energy Engneering, Tohoku University, Assitant Professor, 大学院・工学研究科, 助教授 (60143038)
AKAIZAWA Takashi Institute of Development, Aging and Cancer, Tohoku University, Dept. of Nuclear Medicine and Radiology, Assistant, 加齢医学研究所, 助手 (60302220)
KUBOTA Kazuo Institute of Development, Aging and Cancer, Tohoku University, Dept. of Nuclear Medicine and Radiology, Assistant Professor, 加齢医学研究所, 助教授 (40161674)
ABE Yoshinao School of Medicine, Hirosaki University, Department of Radiology, Professor, 医学部, 教授 (10167950)
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| Project Period (FY) |
1997 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥9,600,000 (Direct Cost: ¥9,600,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1999: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Tumor / Potential doubling time / DNA synthesis / Positron emission tomography / Fluorothymidine / SPECT / ポテンシャル倍加時間 / 二重標識法 / FSa-II / 放射線効果 / PET |
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| Research Abstract |
We optimized a double labeling method using ^3H-thymidine and anti BrdUrd antibodies for measuring potential doubling time (Tpot) of animal tumors. Then, we measured growth kinetics of a mouse tumor after irradiation and found that Tpot values were inhomogeneous within a tumor during fractionated irradiation and that some population grew as rapid as un-irradiated tumors. We could demonstrate the accelerated re-population during irradiation . Such kind information is very important for radiotherapy planning. Tpot measurement in humans by nuclear medicine should be developed.
As tracers for the evaluation of cell proliferation, iodine-labeled uridine derivatives and ^<11>C-thymidines were evaluated from the view point of stability and metabolism in the serum and tissues. These tracers proved not o be suitable for our purposes, because the former is de-iodinated in the blood and tissues and latter is metabolized in the tissues and thus estimation of DNA binding fraction will be very diffic
… More
ult. While ^<18>F-3'-deoxy-3'- fluorothymidine ([^<18>F]FLT) was reported to be stable in the blood and trapped in the proliferating tissues. We decided [^<18>F]FLT is the best tracer for visualizing proliferative activity of tumors in vivo. Then, we tested radiosynthesis of [^<18>F]FLT and evaluated its efficacy for clinical application.
The radiosynthesis was performed according to the literature ; [^<18>F]Fluoride was reacted with the substrate dissolved in acetonitrile at 100℃ for 15 min. After deprotection by addition of cesium ammonium nitrate the crude product was purified by passing through a short column and finally by HPLC separation. The radiochemically pure [^<18>F]FLT was obtained in overall radiochemical yields of 6-8% within 100 min. We concluded that the method was reproducible despite our lower yields compared to the reported value of 13%. Biodistribution studies with rats showed that [^<18>F]FLT was remarkably accumulated in bone marrow as expected. We have already obtained data for exposure dose and acute toxicity from a preceding research group in USA and thus finished the preparation for clinical use of [^<18>F]FLT.However, it should be pointed out that our method based on manual operation must be automated for routine practice and that it requires another investment.
We have also started to develop new ^<18>F-labeled tumor imaging agents, based on analogous design of microtubular and matrix metalloproteinase inhibitors which are closely related to tumor proliferation. Less
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