1996 Fiscal Year Final Research Report Summary
Gadolinium neurton capture therapy for malignant brain tumors
| Project/Area Number |
06454413
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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 |
Cerebral neurosurgery
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
TAKAGAKI Masao Kyoto University Research Reactor Institute, Assistant, 原子炉実験所, 助手 (70252533)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Toru Kyoto University Research Reactor Institute, Assistant Professor, 原子炉実験所, 講師 (90089136)
ONO Koji Kyoto University Research Reactor Institute, Professor, 原子炉実験所, 教授 (90122407)
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| Project Period (FY) |
1994 – 1996
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| Keywords | Malignant brain tumors / Neutron capture therapy / Gadolinium / Boron |
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| Research Abstract |
NCT effect on experimental brain tumors were preliminary investigated using GdDTPA and the theoretical dose distribution was studied. (1) The surviving fraction decreased without a sigmoidal sholder as a fuction of the thermal neutron dose. A 1% survival level was obtained at 3.75E+12n/cm2 for Gd (+) medium and 2.50E+13n/cm2 for Gd (-) medium, obtaining an approximetely 6.7 fold difference. The plating efficiency was 60%. (2) Brain tumor rats received no any treatment were drustically died at 16.4days. There was no significant difference in the survival length between the neutron only and 0.4ml GdDTPA,27days. The significant prolonging life was observed on the 2+1ml GdDTPA,32days. (3) Maximum attainable concentration in human glioblastoma was 142ppm and T/B ratio was 0.54(]SY.+-。[)0.39 (n=10) on our experimental conditions. (4) Seven brain tumor cats showed no neurological deficits during one week observation after GdNCT.No significant damage was observed on the normal bain one week af
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ter GdNCT even on a peripheral parenchyma around a superior saggital sinus. In two cases out of four BT cats one week after GdNCT,tumor disappeared and minimum hemorrhagic necrotic tissue was observed in the domain. One BT cat died during neutron exposure due to ite deep anesthesic condition. One BT cat showed the only partial responce on the pathologial examination. Tumor cells were killed and large number of lymphocyte aggregate surrounding tumors. However vial tumor cells could be seen maily in perivascular region and sometime tumor cuffing could be remained though these tumor cell received strong radiation bombardment due to the higher Gd concentration in the vessels. These vial tumor cells are suspected to be radiation registant. (5) If the T/B ratio of 0.54 was assumed in the cats, Gd concentration in cat brain tumor was approximately 200ppm which almost two fold as that of human glioblastoma. Therefore the required concentration of GdDTPA in human glioblastoma might be hardly attained via GdDTPA regardless its high concentration in blood and toxicity. (6) The fraction of killing effect of Auger and IC is estimated 15%. The large killing effect is associated with gamma rays. Thus, the efficacy of GdNCT is strongly dependent on the tumor size since trajectory of gamma rays is beyond tumor size. This fact is a pit fall in this study using small tumor model of rat brain tumor. Tumor debulking prior to this therapy might not be indicated. This stand point is hardly accepted by many neurosurgeons. The epithermal neutron is essential for GdNCT,since thermal neutrons are easily absorbed in Gd-rich tissue (self-shielding efect). This effect can be alleviated by epithermal neutron irradiation. The optimal Gd concentration in tumor was estimated 200-300ppm from the self shielding effect. Less
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