2001 Fiscal Year Final Research Report Summary
Enhanced Effect of Pharmaceutical on Deposition of Radioactive Bone-seeking Agents in Osteoblasts
| Project/Area Number |
11670874
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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 |
Radiation science
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| Research Institution | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
SETO Hikaru Faculty of Medicine TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY Professor, 医学部, 教授 (20019962)
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| Co-Investigator(Kenkyū-buntansha) |
KAMISAKI Yuichi Faculty of Medicine TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY Assistant, 附属病院, 助手 (30251888)
MIYAHARA Tatsuro Faculty of Pharmaceutical Sciences TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY Associate Professor, 薬学部, 助教授 (10019119)
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| Project Period (FY) |
1999 – 2001
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| Keywords | Bone formation / Fetal osteoblastic cell / Tissue culture / Calcium-45 / Phosphorus-32 / 1.25fOm2D3 (vitamin D3) / F-6-1.25(OH) 2D3 / Vitamin K2 |
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| Research Abstract |
Bone-seeking radiopharmaceuticals have been used as the therapeutic agents to relief intractable bone pain in patients with metastatic bone disease, in which the greater the osteoblastic activity, the greater the concentration of the agents in and about the tumor is observed. Until now, several pharmaceuticals such as vitamin D3, PTH or androgen have been tried to enhance the deposition of radioactive agents, no routine clinical use is, however, available. In this study we assessed the enhanced effect of 26, 27-hexafluoro-1α, 25-dihydroxy vitamin D3 (vitamin F-D3) vitamin K2 on radioactive calcium deposition in osteoblastic cells as compared to the effect of vitamin D3.
Fetal osteoblastic cells (SV-HFO) were cultured for 3 days in a α-MEN medium with 10% fetal bovine serum. Then, β-glycerophosphate (β-GP) and dexamethasone were added to induce the development of ossification. Moreover, vitamin D3, vitamin F-D3, vitamin K2 or both were added to enhance the deposition of calcium in osteob
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lasts. The medium was changed every 2 days. After the observation of ossification, radioactive calcium (Ca-45) was added to the medium, and was cultured for 24 hours. Then, osteoblasts were separated from the culture and radioactivity of Ca-45 in the osteoblasts was measured.
Ca-45 deposition in the osteoblasts increased as the β-GP concentration increased from 0 to 10 mM. Addition of vitamin D3 enhanced the deposition of Ca-45 about 1.4 fold as compared to β-GP only. Moreover, vitamin F-D3 showed a strong enhanced effect on the deposition of Ca-45 about 16.4 fold as compared to β-GP only. Vitamin K2 only showed no enhanced effect on the diposition of Ca-45. No superimposed effect of vitamin K2 on vitamin FD3 was observed to enhance the effect of Ca-45 deposition in the osteoblasts.
A new pharmaceutical, 26,27-hexafluoro-1α, 25-dihydroxy vitamin D3 (vitamin F-D3) has a potential enhanced effect on the deposition of calcium in osteoblasts. This pharmaceutical might be effective in patients with metastatic bone disease and osteomalacia instead of vitamin D3. Less
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