| Project/Area Number |
11670923
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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 | Sapporo Medical University |
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Principal Investigator |
FUJII Hirotada Sapporo Medical University, School of Health Sciences, Professor, 保健医療学部, 教授 (70209013)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIKAWA Kohki The University of Tokyo, Department of Radiology, Associate Professor, 医科学研究所, 助教授 (10272494)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | free radicals / non-invasive visualization / ESR / MRI / spin trapping / NO / T1 |
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| Research Abstract |
The ultimate goal of in vivo electron spin resonance (ESR) spin trapping is to provide a window to the characterization and quantification of free radicals with time within living organisms. However, the practical application of in vivo ESR to systems involving reactive oxygen free radicals has proven challenging. Some of these limitations relate to instrument sensitivity and particularly to the relative stability of these radicals, as well as toxicity limitations with dosing. We have demonstrated a new and first approach, so called MRI spin trapping method, to visualize the distribution of nitric oxide (NO) free radicals. NO was complexed with Fe (II)-chelate spin trap, N-methyl-D-glucamine dithiocarbamate (MGD), verified as (MGD)_2-Fe(II)-NO by ESR, and the distribution of NO was visualized by MRI.In rats, (MGD)_2-Fe(II)-NO complex was concentrated in the liver displaying significantly enhanced contrast in the vascular structure such as hepatic vein and inferior vena cava. Nitric oxide synthase was verified as the source of NO in rats with septic shock by pre-administration of the competitive inhibitor, resulting in reduced enhancement of the MR images. The NO complex was more stable in vivo and a more effective MRI contrast agent than other stable nitrogen containing radicals, such as nitroxides. MRI spin trapping method should be a powerful tool for visualizing spatial distribution of free radicals in tissues when combined with the appropriate spin-trapping agents.
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