2003 Fiscal Year Final Research Report Summary
Basic study of molecular targeting agents for neutron capture therapy
| Project/Area Number |
13671420
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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 |
Cerebral neurosurgery
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| Research Institution | University of Tsukuba |
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Principal Investigator |
MATSUMURA Akira University of Tsukuba, Institute of Clinical Medicine, Professor, 臨床医学系, 教授 (90241819)
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| Co-Investigator(Kenkyū-buntansha) |
TAKANO Shingo University of Tsukuba, Institute of Clinical Medicine, Assistant Professor, 臨床医学系, 講師 (50292553)
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| Project Period (FY) |
2001 – 2003
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| Keywords | neutron capture therapy / boron / BSH / BPA / cell cycle / thiol / gadolinium / malignant glioma / radiation therapy |
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| Research Abstract |
1) cell cycle dependency of boronated compounds
Two boronated compounds used in clinical settings (BSH & BPA) were investigated for its cell cycle dependency. Three cell lines (9L, c&, V-79) were used. The cells were incubated with boronated compounds in logarhytymic growth phase. As the results, BSH showed little cell cycle dependency when compared to BPA by examining the boron concentration after cell sorting by cell cycle using flowcytometry. The absolute cell boron concentration was higher in BPA than BSH. Based on these findings, the clinical application of two compounds may be improved (Yoshida et al. 2002)
2) The uptake mechanism of BSH into the cells
BSH is composed from the carborane cage with a thiol (-SH). We have investigated the intake of BSH into three cell lines in relationship to the depletion of Glutathione (GSH), which is a major thiol compound in the cells. By depleting the GSH using BSO, the uptake of BSH was increased in all three cell lines. The neutron irradiation r
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esulted in stronger killing effect in BSO+BSH than DSH group. The gamma irradiation resulted lower killing effect in BSO+BSH than HSO group. These results indicate that uptake mechanism of BSH may be related to thiol uptake and the BSH may serve as a radioprotectant though its effect is weak
3) Basic study for gadolinium neutron capture therapy (Gd-NCT)
Gd-DTPA has been widely used for MRI contrast agent for CNS disease. We have investigated a new hepatocellular MRI contrast agent (Gd-BOPTA) for possible agent for Gd-NCT. The uptake of Gd-BOYTA into normal hepatic cells are thought to be mediated by molecular mechanism of ATP binding cassette (A.BC) protein. The MRI contrast in rat brain tumor model was superior in Gd-BOPTA than Gd-DTPA and the Gd concentration was higher and retained longer in Gd-BOPTA measured by ICP-AES (Zhang et al. 2002). Based on this result, we have performed a neutron irradiation experiment in rat thigh tumor model of 9L in vivo. The result revealed that Gd-BOPTA showed better tumor control than Gd-DTPA by application of the same amount of Gd into the tumor (Matsumura et al. 2003) Less
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