臺灣博碩士論文加值系統

中 文 摘 要
本研究嘗試以鎝99m標誌三個胺?類化合物作為腫瘤低氧部位造影的研究。三個胺?類化合物包括
DmPn(AO)2，Bn*(AO)2及Bn(AO)2。經自製合成後，以核磁共振光譜、質譜、元素分析等確定化
合物的結構與成份。然後以鎝-99m標誌，再經放射化學分析，包括：萃取效率、電泳動、 薄層
層析、高效液相層析等以了解鎝99m標誌錯合物的標誌效率、親脂性、電性以及純度。在癌細胞
低氧環境吸收試驗及腫瘤小鼠吸收分佈試驗中，接下來將製備的鎝99m錯合物，經萃取，取有機
相以高純氮氣吹乾等過程純化後，加入生理食鹽水調勻，注入低氧環境下的癌細胞培養液，探討
癌細胞隨時間變化對錯合物吸收情形。另以腫瘤小鼠觀察鎝99m-錯合物吸收分佈情形，以了解所
測試錯合物是否有累聚在腫瘤的現象。

Abstract
Alkylene amine oximes including DmPn(AO)2、Bn*(AO) and Bn(AO)2 were synthesized and identified by NMR , Mass , Elemental analysisnts . Subsequently , using trace-level 99mTcO4- from generator was used to label these compounds in the presence of suitable concentration of Sn2+. The 99mTc-amine oxime complexes obtained were radioanalttically characterized simultaneously by solvent extraction , TLC , electrophoresis and HPLC. From the results , the labelling yield , lipophilicity , neutrality and stability of these complexes were realized .
Nfsa cancer cells were utilized as our in vitro experiment''s target and the 99mTc-complexes were injected into the cell culture in hypoxic condition . Uptake of the 99mTc-complexes by the cancer cells versus time was observed . In addition , an in vivo experiment was carried out using C3H/HeN tumor bearing mice . It is indicated from the study that one of the three 99mTc-complexes seems to have the potential to develop as a hypoxia imaging agent.

目 錄
中文摘要‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ Ⅰ
Abstract‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ Ⅱ
謝誌‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ Ⅲ
目錄‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ Ⅳ
表目錄‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ Ⅵ
圖目錄‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ Ⅶ
第一章 緒論
1-1 核醫藥物簡介‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 1
1-2 腫瘤低氧顯影藥物‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 2
1-3 本研究的方向及目的‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 6
第二章 化合物合成與鑑定
2-1 儀器與藥品‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 8
2-2 有機合成‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 9
2-2-1 chloroxime 的合成‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 9
2-2-2 DmPn(AO)2的合成與鑑定‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 10
2-2-3 Bn*(AO)2的合成與鑑定‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 10
2-2-4 Bn(AO)2的合成與鑑定‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 11
第三章 鎝99m錯合物的製備與特性分析
3-1 儀器與藥品‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 23
3-2 鎝99m的配位原理‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 24
3-3 鎝99m與胺?類配位子的錯合‧‧‧‧‧‧‧‧‧‧‧‧‧25
3-4 鎝99m錯合物的特性分析‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 26
3-4-1 溶劑萃取法‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 26
3-4-2 薄層層析法‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 27
3-4-3 電泳動分析法‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 29
3-4-4 高效率液相層析法‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 30
3-5 鎝-99m錯合物萃取的穩定度測試‧‧‧‧‧‧‧‧‧‧‧ 36
3-6 鎝99m錯合物化學特性評估
結果與討論‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 43
第四章 腫瘤細胞與腫瘤小鼠對鎝99m-錯合物之吸收測試
4-1 腫瘤細胞對鎝99m-錯合物之吸收試驗‧‧‧‧‧‧‧‧‧ 47
4-1-1 癌細胞的培養‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 47
4-1-2 癌細胞數目的估算‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 47
4-1-3 癌細胞低氧環境‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 48
4-1-4 低氧環境癌細胞對鎝99m-錯合物之吸收試驗‧‧‧‧‧ 50
4-2 腫瘤小鼠對鎝99m-錯合物之吸收試驗‧‧‧‧‧‧‧‧‧ 51
4-2-1 腫瘤小鼠的培養‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 51
4-2-2 腫瘤小鼠鎝99m-錯合物之吸收之生物分佈試驗‧‧‧‧ 52
4-3 癌細胞與腫瘤小鼠對鎝99m-錯合物之吸收試驗結果與評估52
第五章 參考資料‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ 60

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