請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80922完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 忻凌偉(Ling-Wei Hsin) | |
| dc.contributor.author | Pin-Chen Kuo | en |
| dc.contributor.author | 郭品辰 | zh_TW |
| dc.date.accessioned | 2022-11-24T03:22:05Z | - |
| dc.date.available | 2021-11-08 | |
| dc.date.available | 2022-11-24T03:22:05Z | - |
| dc.date.copyright | 2021-11-08 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-09-27 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80922 | - |
| dc.description.abstract | "古柯鹼是一種中樞神經興奮劑，會與多巴胺競爭多巴胺轉運體的結合位置，間接導致突觸間隙的多巴胺濃度提升，進而使人體產生過度興奮與成癮之效果，也引發許多社會問題，因此有必要開發具有古柯鹼戒斷治療潛力的藥物。先前本實驗室已經合成出一系列新穎GBR12935衍生物作為古柯鹼濫用治療藥物，並從中篩選出針對多巴胺轉運體具有高度親和力、選擇性，以及適當脂溶性的候選藥物：化合物4與化合物5，而目前需要更進一步地探討此二候選藥物在活體內的動態分佈。 傳統藥物動力學進行藥物在體內的分佈研究，必須犧牲大量的實驗動物，而利用正子斷層掃描技術，僅需給予少量的放射性藥物，就能夠以非侵入性的方式獲得實時監測的影像，再透過生物體學影像定量分析軟體將正子斷層掃描影像數據化，計算出標準攝取值 (standardized uptake value, SUV) 與標準攝取值比 (standardized uptake value ratio, SUVR)，即能夠得到客觀且準確的藥物在活體內動態分佈資訊，不僅可以縮減實驗動物的消耗，還能夠使用同一隻實驗動物完成數個時間點的藥物分佈分析。 故本研究中，利用正子斷層掃描技術監測18F-4和18F-5在小鼠全身的動態分佈情形；而紋狀體已被報導具有最高密度的多巴胺轉運體，因此紋狀體將會是本研究中重要的觀察目標之一，藉此判斷放射性追蹤劑是否能夠累積於紋狀體並與多巴胺轉運體選擇性結合。 由PET影像發現，靜脈注射給予18F-4和18F-5的初期，心臟與肺臟的攝取量較高，然後隨著血液循環分佈至肝臟、腸道、腎臟、膀胱等器官；而18F-4在腦部的累積量比18F-5多，代表18F-4的血腦障壁穿透性較好，因此比較容易進入到腦部。在腦部可觀察到18F-4和18F-5選擇性累積於紋狀體，該結果表示此二候選藥物是具有潛力的，有機會發展為後續臨床使用古柯鹼濫用治療的藥物。" | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-24T03:22:05Z (GMT). No. of bitstreams: 1 U0001-1609202116163700.pdf: 33809008 bytes, checksum: e222d4c0a68eb682a0bfc9445464ba61 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | 口試委員審定書…………………………………………………………………………I 誌謝……………………………………………………………………………………...II 摘要…………………………………………………………………………………….III Abstract………………………………………………………………………………...IV 英文縮寫表…………………………………………………………………………….VI 總目錄…………………………………………………………………………………VII 圖目錄………………………………………………………………………………….IX 路徑目錄…………………………………………………………………………….....XI 第一章、緒論……………………………………………………………………….1 1.1 多巴胺之簡介……………………………………………………………1 1.2 多巴胺轉運體與古柯鹼之關係…………………………………………2 1.3 正子斷層掃描簡介與藥物動態分佈研究………………………………4 1.4 研究中之GBR類多巴胺轉運體造影劑………………………………...6 1.5 研究目的與動機…………………………………………………………7 第二章、結果與討論……………………………………………………………….9 2.1 18F-4之正子斷層掃描小鼠全身造影結果…………………………….9 2.2 18F-4之正子斷層掃描大鼠腦部造影結果…………………………...13 2.3 18F-4 displacement study………………………………………………17 2.4 18F-5之正子斷層掃描小鼠全身造影結果…………………………...21 2.5 18F-5之正子斷層掃描小鼠腦部造影結果…………………………...26 2.6 18F-4及18F-5之全身SUV、SUVR比較………………………………30 2.7 18F-4、18F-4 + GBR12909及18F-5之紋狀體SUV、SUVR比較……...35 第三章、結論……………………………………………………………………...38 實驗部份…………………………………………………………………………….....39 一、實驗動物來源…………………………………………………….......…..39 二、一般儀器與方法…………………………………………………………....39 三、實驗方法…………………………………………………………………..39 1. 18F-4之正子斷層掃描小鼠全身造影…………………………………39 2. 18F-4之正子斷層掃描大鼠腦部造影…………………………………40 3. 18F-4 displacement study……………………………………………….40 4. 18F-5之正子斷層掃描小鼠全身造影…………………………………41 5. 18F-5之正子斷層掃描小鼠腦部造影…………………………………41 參考文獻…………………………………………………………………………....42 附表目錄…………………………………………………………………………….....45 附圖目錄…………………………………………………………………………….....48 附圖 (Part I)…………………………………………………………..…………..48 附圖 (Part II)………………………………………………………………...……53 | |
| dc.language.iso | zh-TW | |
| dc.subject | 動態分佈 | zh_TW |
| dc.subject | 正子斷層掃描 | zh_TW |
| dc.subject | 古柯鹼 | zh_TW |
| dc.subject | cocaine | en |
| dc.subject | positron emission tomography | en |
| dc.subject | dynamic distribution | en |
| dc.title | 利用正子斷層掃描進行新穎具古柯鹼濫用治療潛力藥物的活體動態分佈研究 | zh_TW |
| dc.title | In Vivo Dynamic Distribution Study of Novel Potential Cocaine-abuse Therapeutic Agents Using Positron Emission Tomography | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 孔繁璐(Hsin-Tsai Liu),翁啟昌(Chih-Yang Tseng),陳惠亭 | |
| dc.subject.keyword | 古柯鹼,正子斷層掃描,動態分佈, | zh_TW |
| dc.subject.keyword | cocaine,positron emission tomography,dynamic distribution, | en |
| dc.relation.page | 345 | |
| dc.identifier.doi | 10.6342/NTU202103213 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-09-28 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥學研究所 | zh_TW |
| 顯示於系所單位： | 藥學系 | |
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|---|---|---|---|
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