合成與鎝99m標誌IDA衍生物：核子醫學之肝膽造影藥劑

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Title:	合成與鎝99m標誌IDA衍生物：核子醫學之肝膽造影藥劑 Synthesis and 99m Tc Labeling Iminodiacetic Acid Analogues：A Hepatobiliary Imaging Agent in Nuclear Medicine
Authors:	彭肇堯
Contributors:	藥物科技研究所呂玉玲
Keywords:	肝膽造影藥劑核子醫學放射性藥劑 IDA衍生物鎝99m radiopharmaceutical nuclear medicine hepatobiliary imaging agent iminodiacetic acid Tc-99m
Date:	2012
Issue Date:	2013-04-22 16:49:50 (UTC+8)
Abstract:	目前我們設計並合成99mTc標誌IDA化合物7a、7b，這兩個化合物經過體外細胞毒性分析，其數據顯示7a和7b並沒有細胞毒性，可預期它們作為肝膽道造影劑時，應無肝細胞毒性的疑慮。在核子醫學造影上比較三種不同的99mTc-IDA衍生物， 99mTc-7a (8a)、 99mTc-7b (8b) 和99mTc-Hepatolite® 於配製後，藉由動物實驗進行體內之生物分佈的評估。注射放射性目標複合物99mTc-7a (8a) 到兔子體內，進行連續靜態造影掃描，發現8a在肝臟的放射性活度比心臟或腎臟高，這個結果清楚地表示目標化合物7a能選擇性分佈到肝膽系統裡。相較之下，放射性目標複合物99mTc-7b (8b) 分佈到肝臟的比率很低，因此目標化合物7b是不適合作為肝膽道造影劑。雖然，99mTc-7a (8a) 的選擇性肝臟分佈並未優於市售藥劑99mTc-Hepatolite®，但是在肝臟的放射性活度比在心臟或腎臟，有高達六倍以上。在本研究中，我們開發出二苯胺基這類新的肝膽系統之原型先導化合物，未來在7a的二苯結構上進行親電子性取代質子反應的修飾，期待它增加選擇性分佈到肝膽系統的能力，成為提供完美的肝膽道造影之候選藥物。 In the present study, we design and synthesized of 99mTc labeling IDA compounds 7a and 7b. In vitro cytotoxicity assays of these compounds, data showed that 7a and 7b were nontoxic for various cancer cell lines. Therefore, we did not warred about hepatotoxicity as a hepatobiliary imaging agent. For a nuclear medicine imaging comparison, three different 99mTc-IDA derivatives, 99mTc-Hepatolite®, 99mTc-7a (8a) and 99mTc-7b (8b), were prepared and evaluated for their in vivo biodistribution through animal models. Serial static image scans of rabbits injected with 99mTc-7a (8a) revealed that higher radioactivity concentrations of the liver compared to the heart or kidneys. This result clearly showed that 7a showed selective distribution to the hepatobiliary system. In contrast, the distribution ratio of 99mTc-7b (8b) was low level to the liver, hence 7b is not suitable as a hepatobiliary imaging agent. Although, the liver selective of 99mTc-7a (8a) has not better than commercial source (99mTc-Hepatolite®), the radioactivity of the live also show six fold difference than the heart or kidneys. In this study, we developed a novel aimnobiphenyl as prototypical lead compound for hepatobiliary system. We further modify 7a via electrophilic substitution protons of biphenyl ring, expect for selective distribution to the hepatobiliary system, the further may be provide a perfect candidate for hepatobiliary imaging.
Relation:	校內校外均不公開，學年度：100，104頁
Appears in Collections:	[Dept. of Pharmacy] Dissertations and Theses

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