| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Hisataka Kyoto University, Assistant Professor, 医学研究科・映像医療学, 助手 (60311734)
FUKUDA Satoshi National Ingtitute Radiolog Sciences, Researcher, 放射線医学総合研究所, サブグルブリーダ研究職 (30165287)
SAKAHARA Harumi Hamamatsu University Shcool of Medicine, Professor, 教授 (10187031)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
Advances have been made in cancer therapy that prolong life expectancy, however, in primary bone tumor or bone metastases, the presence of pain, compromise patients' quality of life. Progress on bone research indicates presence of bone resorption and formation types of osteoclastic (OC) and osteoblastic (OB) metastases, respectively. Early differential diagnosis of bone metastases is desirable but radiotherapeutical agent would help a breakthrough to cancer pain palliation. In the applicant laboratory, a new pH sensitive tumor agent, the polynuclear pentavalent technetium-99m complex of dimercaptosuccinic acid (^<99m>Tc (V)-DM) has been developed and clinical trials indicated its accumulation in bone tumors, bone metastases, Paget's diseases. On those basis, synthesis of a therapeutical agent with a Tc congener, the beta emitter, rhenium-186 (Re-186) was estimated. Studies on various labeling parameters, made the ^<186>Re (V)-DMS available, and its longer half-life allowed basic histom
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orphological studies. Then, to learn about the pH sensitive ^<99m>Tc (V) -DMS character, biodistribution changes in mice under variable conditions of acidosis, induced by glucose or ammonium chloride were compared with the conventional bisphosphonated Tc-bone agent (Tc-BP). Response on radioactivity bone uptake, detected only with ^<99m>Tc (V)-DMS ; autoradiographic and histological bone tissue studies revealed high radioactivity regions overlaying osteoclastic activity rich areas. Further studies on cultured bone cells, namely, OC and OB cells showed, 10-50 times higher accumulation of ^<99m>Tc (V)-DMS in OC than OB cells, with Tc-BP accumulated in OB cells although at low rate. Significant effect of acid pH incubation media detected only with ^<99m>Tc (V) -DMS.Thus, characterization of its uptake mechanism using various cell membrane transport system inhibitors revealed the involvement of Cl-/HCO3-exchanger and phosphate transporter system. The gathered data during the provided grant offered basic in-vivo and in-vitro knowledge for understanding clinical bone disease problems, related to OC, opening a road not only to new diagnostic resources for osteolytic metastases but a breakthrough to bone pain palliation in cancer patient. Less
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