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題 名 | 鎝-99m-HYNIC-Herceptin之穩定性與有效性評估:體外研究=Evaluation of Stability and Efficacy of □Tc-HYNIC-Herceptin: An In-Vitro Study |
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作 者 | 詹繕合; 蔡世傳; 吳裕隆; 葉忠興; 羅彩月; 林萬鈺; | 書刊名 | 核子醫學雜誌 |
卷 期 | 23:2 2010.06[民99.06] |
頁 次 | 頁85-91 |
分類號 | 418.31 |
關鍵詞 | 乳癌; 人類表皮生長因子受體-2; 體外穩定性; 體外有效性; 鎝-99m-HYNIC-Herceptin; Breast cancer; Human epidermal growth factor receptor-2; HER2; In-vitro stability; In-vitro efficacy; □Tc-HYNIC-Herceptin; |
語 文 | 中文(Chinese) |
中文摘要 | 背景:人類乳癌病灶若具有人類表皮生長因子受體-2(HER-2)表現時,通常生長快速,復發率高,對傳統化療效果差且存活期短。新上市的標靶治療藥物Trastuzumab (Herceptin)對具有HER-2高表現之乳癌有相當好的療效。然而根據統計只有約30%乳癌病患具有HER-2表現,因此治療前確認乳癌是否有HER-2表現十分重要。目前臨床多用免疫組織化學染色法(immunohistochemistry; IHC)和原位螢光雜交法(fluorescence in situ hybridization; FISH)來評估HER-2之狀態,此二法不但昂貴、且須以侵犯性方法取得組織樣本。近期核研所研發鎝-99m-HYNIC-Herceptin,希望能以核醫影像取代此二法。本研究針對核研所研發之鎝-99m-HYNIC-Herceptin進行體外穩定性(標幟效率)及有效性評估,以作爲未來進行體內動物實驗之塞礎。 方法:鎝-99m-HYNIC-Herceptin在室溫下以等量生理食鹽水與在37℃下與等量人類血漿充分混合,分別於5分鐘、30分鐘、1、2、3、4、5、6、7、8及24小時後採樣分析其標幟效率。另將具有HER-2高表現之BT-474人類乳癌細胞株與低表現之MCF-7人類乳癌細胞株分別與鎝-99m-HYNIC-Herceptin混合,經過5分鐘、1、4、24,少時後分析鎝-99m-HYNIC-Herceptin與人類乳癌細胞株結合的比率。 結果:鎝-99m-HYNIC-Herceptin不論與生理食鹽水或與血漿混合,其標幟效率一直都能維持在90%以上。鎝-99m-HYNIC-Herceptin與兩株人類乳癌細胞株(BT-474與MCF-7)的接合程度呈現明顯差異;鎝-99m-HYNIC-Herceptin對於BT-474具有高的專一性,結合比例一直維持在70-80%之間;反之,鎝-99m-HYNIC-Herceptin與MCF-7結合率明顯較差,其結合比例約爲30-35%。 結論:核研所發展之鎝-99m-HYNIC-Herceptin其體外穩定性良好,即使與人類血漿混合經過24小時仍有90%以上之結合率。鎝-99m-HYNIC-Herceptin在體外對人類乳癌細胞株,亦可精確反映HER-2表現高低之不同。此結果可作爲未來進行動物體內實驗之依據。 |
英文摘要 | Background: A breast cancer with human epidermal growth factor receptor-2 (HER-2) expression usually presents rapid growth of tumor cell, high recurrence rate, poor response to traditional chemotherapy and poor survival rate. The new release of a targeted-therapy drug, Trastuzumab (Herceptin), brings the great hope to these patients. However, only 25%-30% patients with HER2 gene will response to this drug. Trastuzumab is quite expensive and has certain side effect. Therefore, it is very important to make sure if the patients have the expression of HER2 before prescription of this drug. Two common methods including immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are used for the evaluation of HER-2 expression currently. Both methods are invasive and need tissue sample from tumor via biopsy. Institute of Nuclear Energy Research (INER) has successfully developed (superscript 99m)Tc-HYNIC-Herceptin lately. There are many advantages for a scintigraphy in the evaluation of HER-2 including non-invasive, whole-body scanning, and semi-quantitative. In this study, we evaluated the in-vitro stability and effectiveness of (superscript 99m)Tc-HYNIC-Herceptin. Methods: (superscript 99m)Tc-HYNIC-Herceptin was mixed with same volume of normal saline under room temperature. Labeling efficiency at 5 mm, 30 mm, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h and 24 h was determined. The labelling efficiency at the same time points was also checked when (superscript 99m)Tc-HYNIC-Herceptin was mixed with same volume of human plasma at 37 C. (superscript 99m)Tc-HYNIC-Herceptin was mixed with BT-474 cells (high HER-2 expression human breast cancer cell) and MCF-7 cells (low HER-2 expression human breast cancer cells) and the binding of (superscript 99m)Tc-HYNIC-Herceptin to the tumor cells at 5 mm, 1 h, 4 h and 24 h was measured. Results: The labeling efficiency of (superscript 99m)Tc-HYNIC-Herceptin was greater than 90% either in normal saline or in human plasma. (superscript 99m)Tc-HYNIC-Herceptin showed high binding to BT-474 cells (70-80%) and low binding to MCF-7 cells (30- 35%). Conclusion: The (superscript 99m)Tc-HYNIC-Herceptin developed by INER has very good in-vitro stability. Its labeling efficiency can maintain above 90% even at 24 h after mixed with human plasma. In addition, (superscript 99m)Tc-HYNIC-Herceptin produced by INER can also accurately reflect the expression of HER-2 in tumor cells. These results are very encouraging and can be the good foundation for future animal study. |
本系統中英文摘要資訊取自各篇刊載內容。