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題 名 | 放射性同位素治療劑錸-188-錫-1,1-羥基亞乙基二磷酸鹽之體外特性分析與生物體分佈研究=Biodistribution Study and Characteristic Analysis of Rhenium-188-Sn-1,1-Hydroxyethylidene Diphosphonate in Radionuclide Therapy for Nuclear Medicine |
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作 者 | 丁慧枝; 曾誠齊; 丁幹; 謝柏滄; 黃英峰; 李全孝; 劉怡慶; | 書刊名 | 核子醫學雜誌 |
卷 期 | 13:3 2000.09[民89.09] |
頁 次 | 頁157-164 |
分類號 | 418.346 |
關鍵詞 | 放射核種治療製劑; 錸-188-錫-HEDP; 骨轉移; 生物分佈; 體外特性分析; Radionuclide therapy; 188Re-Sn-HEDP; Bone metastasis; |
語 文 | 中文(Chinese) |
中文摘要 | 背景:放射性核種治療劑錸-186-錫-1,1-羥基亞乙基二磷酸鹽(錸-186-錫-HEDP)是目前骨骼轉移癌症骨痛患者最新的治療制劑之一。由於國內尚無法生產高比活度之錸-186放射性同位素及其治療製劑,本研究藉由核能研究所與美國橡樹嶺國家實驗室合作研製的發生器提供錸-188,研製與錸-186-錫-HEDP類似的錸-188-錫-HEDP製劑,進行體外特性分析與生物體分佈研究,以評估銇-188-錫-HEDP作為骨骼轉移癌症骨痛舒緩劑及癌症治療之可行性。 方法:錸-188-錫-HEDP之製備係以自製標幟用乾燥小瓶(內含不同比例的Na2/H2-HEDP、氯化亞錫和龍膽酸抗氧化劑),加入1毫升的錸-188-過錸酸鈉,在98-100℃下加熱約10分鐘,調整溶液pH值至3~11之間。使用以TSK G2000 PW size exclusion gel和Aminex A28陰離子交換樹脂管柱分離錸-188-HEDP配劑出來的五種主要組成成份,經矽膠管柱掃描方法評估錸-188-錫-HEDP之蛋白質結合量及以正辛醇╱緩衝液分配係數評估親脂性大小。以Wistar大白鼠進行生物體分佈實驗及以家兔進行影像分析。 結果:將TSK G2000 PW管柱及Aminex A28陰離子交換樹脂管柱分離錸-188-錫-HEDP製劑出來的五個主要成份進行體外特性分析,其蛋白質鍵結量除了管柱滯留時間最長的第五成份約為2%外,其餘成份均無蛋白質結合量;正辛醇╱緩衝液分配係數log P值約在-1.9至-3.2之間。當標幟配劑pH值高於11以上時,只呈現一種主成分且無蛋白質結合量;正辛醇╱緩衝液之分配係數log P值約為-3.7。實驗結果也顯示標幟pH值愈低時出現的成分就愈多,且幾乎無蛋白質結合量。以Wistar大白鼠進行生物體分佈,結果發現使用TSK G2000 PW size exclusion gel管柱分析所得五個主成份及使用Aminex A28陰離子交換樹脂管柱分析所得五個主要成份中均以第二個成份有較高的骨骼吸收。 結論:由實驗結果得知,放射性核種治療製劑錸-188-錫-HEDP配劑之配製酸度條件以pH值大於7為佳。 |
英文摘要 | Background: 186Re-1, 1-hydroxyethylidene diphosphonate has been used for the palliative treatment of metastatic bone pain. Bone is the most common site of metastatic in breast cancer patients. It is important to consider whether more lasting relief of pain can be accomplished with higher dosage of 186Re-1, 1-hydroxyethylidene diphosphonate. However, it has been difficult to produce 186Re-1, 1-hydroxyethylidene diphosphonate with high specific activity in Taiwan. In our laboratory, we use the 188W/186Re generator provided by the Institute of Nuclear Energy Research. The goal of this study was to analysis and characterize the agent of 188Re-1, 1-hydroxyethylidene diphosphonate, and to study the therapeutical effect of different condition of 188Re-1, 1-hydroxyethylidene diphosphonate. Methods: 188Re-Sn-HEDP was prepared by reconstitution of a kit of lyophilized mixture of Na2/H2-HEDP, SnCl2 2H2O and gentisic acid with 1 ml of 188Re-NaReO4 in saline. The 188Re-Sn-HEDP was formed by reduction of Re (VII) with stanneous ion and brief heating (10 min at 98-100℃), the pH value of resulting solution was adjusted to 3~11. Results: Protein binding of 188Re-Sn-HEDP was evaluated in vitro by gel column scanning method (GCS), the 188Re-Sn-HEDP mixtures which were separated into five components using TSK G2000 PW size exclusion gel and Aminex A28 exchanger resin showed poor binding to HAS (human serum albumin). The partition coefficient, log P1 measured by mixing 20 μl of the 188Re-Sn-HEDP mixture using the above same method with 2 ml each of 1-octanol and buffer (pH 7.0 and 7.4) in a test tube was between -1.9 and -3.2. The only one component of the 188Re-Sn-HEDP above pH=11 eluted from HPLC had lower log P (log P=-3.7). Conclusion: Our study suggests that the optimal pH for the preparation of 188Re-Sn-HEDP is >7. |
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