| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
Hypoxic cells distributed unevenly through tumors are believed to be the primary determinants in resistance to radiation therapy and chemotherapy. It is thought that if tumors are left in a state of hypoxia for an extended period, their malignancy, in terms of proliferative or metastasizing potential, will increase due to vascular endothelial growth factor and other factors. Here, we developed a method for measuring the hypoxic state of tumors in which hypoxic cells are imaged via the hypoxic cell markers that characterize them. We then used this method as an addition to the previously developed 31P-MRS and MRI methods to develop a type of missile therapy targeting hypoxic cells, to conduct positron-based diagnosis using hypoxic cell markers labeled with nuclides such as 64Cu and 67Cu, and to develop a new method of cancer therapy through the combination of hypoxia-targeting missile therapy with a molecular-targeted drug that inhibits neoangiogenesis. As part of our experiments, we implanted SASneo cells with normal p53 and SASmp cells, which have an abnormality in p53. The SASmp cells showed a faster rate of proliferation and a greater tendency to necrotize than the SASneo cells. On injection of 67-Cu-ATSM into the caudal vein of these mice, distribution of RI at 1 and 24 hours after injection was relatively high in parenchymal organs such as the liver, kidneys, and lungs, with relative distribution rates to a plasma rate of 1 of 5.15, 2.33, and 2.32, respectively. In contrast, accumulation in the central nervous system was low, with a distribution rate of only 0.67. RI accumulation did not differ between SASmp and SASneo. Autoradiography of the excised tumors showed 67-Cu-ATSM accumulation in the peripheral portions of tumors. Further, the rate of delay in tumor growth following the injection of isotopes at therapeutic concentrations revealed that growth inhibition tended to be greater in SASneo cells than in SASmp cells.
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