多功能診療用化合物TTDA-NP-b-lapachone之合成及應用研究

Abstract

磁振造影(Magnetic Resonance Imaging，MRI)和核醫藥物(Nuclear Medicine)在近年來已成為一門重要診斷工具。由於Lapachone 為新穎之抗腫瘤藥物，對人類大部分惡性腫瘤具有特殊的抗癌活性，故本實驗室積極設計具有造影效果之前驅藥物，將Lapachone 與本實驗之NP-TTDA配位子及其衍生物接連，再與鑭系金屬、64Cu、99mTc或111In合成磁振造影及核醫造影所需之造影對比劑，目的使其有治療及診斷之功用。本研究主要為設計及合成新型前驅藥物且可為磁振造影對比 劑及核醫造影劑，並探討鑭系金屬、64Cu、99mTc或111In金屬錯合物特性。利用不同溫度下17O NMR所求得的數據以求得釓金屬錯合物之內層水分子交換速率，瞭解此參數對弛緩率(r1)值的影響。最後將合成出之磁振造影對比劑及核醫造影劑，藉由體外細胞影像實驗，探討其是否可目標化至標的位置，達成顯影效果。

Recently, magnetic resonance imaging (MRI) and nuclear medicine have become the leading tools for imaging fine details of anatomy as well as physiology. We design actively a new pro-drug due to lapachone that have special anticancer activity to human most malignant tumor are novel antineoplastic drug. The purpose of this study is to design and synthesize new pro-drug with NP-TTDA or derivatives for MRI and nuclear medicine, and characterize its Gd(III), Eu(II), 64Cu, 99mTc or 111In complexes. The exchange rate between inner sphere water and bulk water will also studied using temperature dependence of relaxivity by 17O NMR technique for Gd(III) complex. Hence, we use lapachone as a probe to conjugated with Gd-complex and targeting specific cell receptor.