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    請使用永久網址來引用或連結此文件: https://ir.cnu.edu.tw/handle/310902800/22494


    標題: 活化焠熄的紅外葡萄糖酸甘前驅探針與前驅抗癌藥物以結合葡萄糖酸表現腫瘤之即時造影與治療
    Real-Time Cancer Imaging and Therapy by Targeted Activation of Self-Quenching Near-Ir Glucuronide Proprobe and Prodrug
    作者: 呂玉玲
    鄭添祿
    貢獻者: 藥學系
    日期: 2009
    上傳時間: 2010-03-26 16:45:40 (UTC+8)
    出版者: 台南縣:嘉南藥理科技大學藥學系
    摘要: 在癌症治療過程中,若有即時影像呈現腫瘤治療的效率,對於治療計劃的修正是非常重要的工具。本計劃想利用β-glucurinidase(βG)來照影及活化葡萄糖醛酸前驅藥物。在我們先前的研究中,利用抗體攜帶βG酵素及基因表現βG酵素合併葡萄糖醛酸前驅藥物的治療模式,βG酵素都能選擇性的在腫瘤部位活化葡萄糖醛酸前驅藥物。最近,我們利用葡萄糖醛酸螢光劑( fluorescein di-β-glucuronide, FDGlcU)的前探針,証實它可以在活體中評估βG的活性。可惜只能對皮下表現的腫瘤有顯影但對轉移的癌細胞卻不能顯現, 可見fluorescein其螢光的訊號不能穿透細胞,為了提昇訊號對細胞穿透力,本計劃想利用激光波長在近紅外線的探針,來增加細胞穿透力,合成葡萄糖醛酸近紅外線(IR-820 glucuronide)的前探針。另外,利用自我焠熄的作用,設計合成雙近紅外線葡萄糖醛酸(Di-IR-820 glucuronide)前探針來增加靈敏性, 降低背景干擾。計劃利用這些前探針評估是否可以作為即時影像照影的顯影劑。並合併用於葡萄糖醛酸前驅藥物的治療模式評估治療的效益。
    Real-time imaging the therapeutic efficacy of cancer in orthotropic animal model is very important in optimization of cancer therapy protocols. To this aims, a ßG memzyme has been used both for imaging and efficient prodrug conversion. Our previous results shown that ßG can selectively activate glucuronide prodrug to produce antitumor activity in antibody-directed enzyme prodrug therapy (ADEPT) and gene-directed enzyme prodrug therapy (GDEPT). Recently, we also demonstrated that a fluorescent glucuronide probe (fluorescein di-β-D-glucuronide, FDGluc) can assess βG activity in vivo. The FDGluc probe, however, only allowed imaging of subcutaneous βG-expressing tumors but not metastatic tumors, indicating the poorly penetrative fluorescein (ex: 495 nm, em: 525 nm) is not adequately sensitive for imaging deeper tissues. Based on these results and problems, develop a fluorogenic imaging agents, which emitting in the near-infrared, will be predicted to improve the problems. So, the project propose to develop self-quenching near-IR (>800 nm) glucuronide proprobe to improve tissue penetration. The utility of self-quenching near-IR (>800 nm) glucuronide proprobe will be assessed in vitro and in vivo. We also purpose to real time imaging the therapeutic efficacy of prodrug in orthotopic liver tumor in vivo by the activation of self-quenching near-IR glucuronide proprobe. Positive results of this strategy will provide a novel method for real-time imaging of βG activity to personalize glucuronide prodrug treatment, allowing optimization of the protocols for selective cancer chemotherapy.
    關聯: 計畫編號:NSC98-2320-B041-003
    顯示於類別:[藥學系(所)] 科技部計畫

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