設計合成B-葡萄糖醛酸酶活化標定之分子探針

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Title:	設計合成B-葡萄糖醛酸酶活化標定之分子探針 Design and synthesis of activity-based trapping for β-glucuronidase
Authors:	黃義賢
Contributors:	呂玉玲嘉南藥理科技大學：藥物科技研究所
Keywords:	B-葡萄糖醛酸酶 β-glucuronidase gene delivery
Date:	2010
Issue Date:	2010-12-30 15:34:15 (UTC+8)
Abstract:	在臨床癌症治療過程中，B-glucuronidase (BG) 應用於報告基因和專一性水解前驅藥物上，具有可行性潛在的吸引力，且在影像顯影上，有利於監測報告基因的表現和前驅藥物治療。在本篇研究中，我們發展出一124I tyramine-difluoromethylphenol glucuronide 分子影像探針 (124I-TrapG) ，它能專一性的被β-葡萄糖酸苷酶所活化，而釋出含 fluorodiene 基團具有親電能力的124I-Trap，能夠與BG表現的癌細胞親核 (nucleophile) 部位形成共價鍵結，以微正電子發射型斷層 (PET) 照影，體內外試驗的結果顯示，124I-Trap的影像訊號表現量確實的累積在有表現β-葡萄糖酸苷酶的CT26腫瘤上，而不表現BG的CT26腫瘤則沒有訊號，如此證實124I-TrapG可以於體內外呈現BG分佈位置及表現量。綜和以上的結果我們可以知道，利用此分子影像探針及微正電子發射型斷層儀，可以偵測活體內腫瘤表現β-葡萄糖酸苷酶的量，未來也可應用於臨床上，來偵測β-葡萄糖酸苷酶表現量來追蹤腫瘤惡化過程，或者評估抗癌治療的成效。 B-glucuronidase (BG) is both an attractive reporter gene and a promising prodrug-converting enzyme for cancer therapy.。Imaging of BG activity in living animals would be a convenient method to monitor reporter gene expression and BG prodrug treatments. In this report, we developed a 124I tyramine-difluoromethylphenol glucuronide probe (124I-TrapG) that could be converted by BG to release a trapping 124I-difluoromethylphenol moiety to crosslink any nucleophile moiety on cells. Enhanced signals were shown in CT26/mBG-eB7 tumors in our micro-PET imaging studies, however CT26 tumors are not, indicate 124I-Trap could present the distribution and expression of BG in vitro and in vivo. According to the result, we could use molecular imaging probes and micro-PET to detect the expression of BG in tumor cells. Also application in clinic, we could trace the tumor progression, or estimate the result of anticancer therapy in future.
Relation:	校內校外均不公開，學年度：98，60頁
Appears in Collections:	[Dept. of Pharmacy] Dissertations and Theses

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