正子斷層掃描造影劑合成

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Title:	正子斷層掃描造影劑合成
Other Titles:	Synthesis of potentially positron emission tomography active compounds
Authors:	林勇宇;Lin, Yung-Yu
Contributors:	淡江大學化學學系碩士班李世元
Keywords:	正子斷層掃描;造影藥物;Positron Emission Tomography;18F-NFP;Arginine -Glycine - Aspartic
Date:	2016
Issue Date:	2017-08-24 23:38:39 (UTC+8)
Abstract:	正子斷層掃描造影是一種核子醫學檢驗技術，目前正子斷層掃描造影可用於觀察細胞代謝、蛋白質的合成和神經傳遞功能，診斷腫瘤、心血管、神經與精神性疾病，並給予正確的治療方法。另外，為使正子斷層掃描造影成像更為精準，必須根據檢測部位給予相對的造影藥物，因此造影的藥物在開發及研究是此造影技術相當重要的環節。目前的腫瘤診斷幾乎都是先用正子斷層掃描造影來做初步的診斷。利用腫瘤細胞會大量吸收葡萄糖的特性，以氟-18標記的去氧葡萄糖來當做造影藥物，但由於正常細胞也會吸收葡萄糖，便會產生偽陰性或偽陽性的成像結果，造成判斷上的困難。血管生成是另一項腫瘤生長和轉移不可或缺的生物過程，藉此可以利用放射性藥物標記來更準確的診斷腫瘤的生長情形。整合素αvβ3受體存在於新生血管内皮细胞和多種腫瘤细胞表面，在血管生成中扮演著關鍵的角色，而精氨酸-甘氨酸-天冬氨酸（Arg-Gly-Asp，RGD）肽可以與整合素αvβ3結合，並具有專一性。因此，我們設計與合成非放射性藥物的4-nitrophenyl-2-fluoropropionate ( NFP )化合物來做為合成氟-18的4-nitrophenyl- 2-[18F]fluoropropionate化合物的測試，作為合成放射性RGD的前驅物。本論文中，第一部份利用亞硫醯氯來製備氯化醯氯，在與醇反應而得到目標產物。第二部分則是利用1-(3-Dimethylaminopropyl)-3-ethyl-carbodiimide ( EDC )和N, N''-Dicyclohexylcarbodiimide ( DCC )進行酯化反應，而得到目標產物。 The Positron Emission Tomography (PET) is a nuclear medical inspection technology. Recently, it was further applied to observe the cell metabolism, protein synthesis and psychiatric diseases and to find out proper treatments for some diseases. Making PET more accurate for detecting tumor growth scenario diagnosis, it is widely used PET for tumor imaging technology which is based on normal cells can absorb. glucose and them accumulate to certain level that PET really detects. Thus, PET way play a key role in drugs research and development. The integrin avb3 receptor relies on the surface of tumor angiogenesis endothelial cells and the tumor cells. It has been confirmed that the integrin avb3 receptor plays an important role of angiogenesis. Therefore, we design and synthesis non-radiopharmaceutical 4-nitrophenyl-2-bromopropionate (NBP) compound as precursor of radiolabelled 4-nitrophenyl-2-[18F]Fluoropropionate (18F-NFP) compound. Both NBP and NFP could be easily synthesized by amidation reaction of α-halopropionate with p-nitrophenol by using 1-(3-Dimethylaminopropyl)- 3-ethyl-carbodiimide ( EDC ) as coupling reagent
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