| Project/Area Number |
06671411
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
IMAHORI Yoshio Kyoto Prefectural University of Medicine, Neurosurgery, Assistant Professor, 医学部, 助手 (80191899)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1994: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | signal transduction / glioma / phosphoinositide turnover / positron emission CT / diacylglycerol / proliferation potential / second messenger / brain tumor / [^<11>C]diacylglycerol / pl代謝回転 |
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| Research Abstract |
We synthesized carbon-11-labeled diacylglycerol (^<11>C-DAG) to investigate the proliferation potential in patients with glioma. The tumor selectivity of ^<11>C-DAG was demonstrated by the analysis of 7 cases of gliomas, using positron emission tomography and usefulness of the tracer was demonstrated. The accumulation of ^<11>C-DAG was found to correlate with the degree of malignancy, suggesting acceleration of phosphoinositide turnover in the malignant group. The T/N ratio in malignant cases, which showed high proliferative state, was higher than low grade glioma cases. The T/N ratio is from 1.5-2.2 in the malignant guoup. Thus cases can be regarded as being benign group if the T/N ratio is lower than 1.5.
Rapid incorporation of the ^<11>C-DAG was observed in the C6 glioma cell line. The incorporated lipid fracton consisted chiefly of phosphoinositide pool and another phospholipid pools in the prolifevative state. When the state was inhibited by (-) -3D-3-deoxy-3-fluoro-myo-inositol, i
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ncorporation into the phosphoinositide pool decreased selectively. This suggested that phosphoinositide turnover is the leading regulator of tumor proliferation potential and showed that ^<11>C-DAG is to be a specific probe for visualizing the tumor signal transduction in vivo.
When we evaluated the efficacy of boron neutron capture therapy using ^<18>F-FDG and ^<11>C-DAG in a patient with glioblastoma who was suffered from massive local brain edema 10 month after neutron irradiation, ^<18>F-FDG study did not show positive image. So we made a diagnose of the radiation injury. On the other hand ^<11>C-DAG study showed a hot area in the same period. The follow-up studied showed a massive expansion of the tumor as like as the accelerated repopulation. Thus we recognized the tumor recurrence in this patient.
In conclusion, 1,2- [^<11>C] DAG served as a probe for the rapid metabolism which occurs in PI turnover. The general elevation in 1,2- [^<11>C] DAG incorporation made it possible to visualize the status of in vivo tumor signal transduction for the proliferation potential using positron emission tomography. We demonstrated the first informative case of glioma. The tumor image obtained by DAG-PET can be of great value for the diagnosis fo brain tumors. Less
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