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研究生:李柔玫
研究生(外文):ROU-MEI LI
論文名稱:利用微小型單光子放射電腦斷層攝影合併電腦斷層觀察[123I]ADAM於大白鼠腦中對血清素轉運體之活體造影
論文名稱(外文):In Vivo Imaging of Serotonin Transporters with [123I]ADAM Micro-SPECT/CT in Rat Brain
指導教授:馬國興馬國興引用關係
指導教授(外文):KUOH-SING MA
學位類別:碩士
校院名稱:國防醫學院
系所名稱:生物及解剖學研究所
學門:生命科學學門
學類:生物訊息學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:71
中文關鍵詞:微小型單光子放射電腦斷層攝影合併電腦斷層
外文關鍵詞:micro-single photon emission computed tomography/computed tomographymicro-SPECT/CT
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血清素轉運體 (serotonin transporters, SERT) 為目前診斷憂鬱病症的重要指標。而其異常可能導致許多神經精神的症狀以及神經學的疾病。因此若能進一步了解腦中血清素轉運體的狀態,則這些訊息將可以提供病人進一步的治療方針。在本實驗中為進行一系列的藥理學研究,用以評估微小型單光子放射電腦斷層攝影合併電腦斷層 (micro-single photon emission computed tomography/computed tomography, micro-SPECT/CT ) 設備造影之可行性。實驗目的為:一、建立micro-SPECT/CT系統對腦造影的標準作業流程。二、利用micro-SPECT/CT設備配合平行孔準直儀 (parallel hole collimator) 觀察 [123I] ADAM於大白鼠腦中之活體造影,並進行影像的擷取、重組以及分析。三、評估並確認 [123I] ADAM利用micro-SPECT/CT設備觀察不同劑量之抗憂鬱藥物─帕羅西汀 (paroxetine),以及5,7-雙羥色胺 (5,7-dihydroxytryptamine, 5,7-DHT) 縫核損傷動物模式中血清素轉運體的分佈情形。四、利用自動放射攝影 (autoradiograpahy)、免疫組織化學染色 (immunohistochemistry)、以及磁振造影 (magnetic resonance imaging, MRI) 進一步確認 [123I] ADAM在使用micro-SPECT/CT 設備的造影中,其藥物分佈情形是否相符。結果顯示:由免疫組織化學染色的結果中,確實可在大白鼠腦的縫核區域發現有許多血清素轉運體存在。[123I]ADAM於正常大白鼠腦中無論是利用micro-SPECT/CT設備或自動放射攝影的實驗中均具有高活度的表現。而在給予靜脈注射帕羅西汀,以及5,7-雙羥色胺損傷模式中,由影像結果顯示出 [123I]ADAM於大白鼠各個腦區均有顯著減少的情形。綜合上述結果,一、確實建立了micro-SPECT/CT 設備對腦造影的標準作業流程;二、 藉由micro-SPECT/CT造影、自動放射顯影、以及免疫組織化學染色結果,證實[123I]ADAM確實是一具有高專一性標示血清素轉運體的核子醫學造影新藥。
Serotonin transporters (SERT) are target sites for many antidepressants. Its abnormalities have been suggested in several neuropsychiatric disorders and neurological disease. Therefore, it is important for understanding the status of SERT and that the information may provide critical information for patient management. In this study, we perform a series of pharmacological studies to validate micro-single photon emission computed tomography/computed tomography (Micro-SPECT/
CT) image. The experimental aims: 1) set up a standard procedure of Micro-SPECT/CT system for brain imaging, 2) The acquisition, reconstruction and analysis of [123I]ADAM Micro-SPECT/CT will be performed using parallel hole collimators, and 3) evaluate the validation of [123I]ADAM micro-SPECT/CT in different dose of SSRIs ─ paroxetine occupancy and serotonergic lesioned models by 5,7-dihydroxytryptamine (5,7-DHT). 4) the autoradiography, immuno- histochemistry and magnetic resonance imaging (MRI) study will be performed to verify the usefulness of [123I]ADAM micro-SPECT/CT. The results showed a large number of SERT in the raphe area in immunohistochemistry study. And the high selectivity of [123I]ADAM in the normal rat brain in [123I]ADAM micro-SPECT/CT and autoradiography studies. After injected intravenously paroxetine or injected intracerebrally 5,7-DHT into the rats, the [123I]ADAM uptake was significantly reduced in almost all the brain regions. In conclusion: 1) we set up a standard procedure of Micro-SPECT/CT system for brain imaging. 2) we proposed that the novel ligand [123I]ADAM can be highly selective for SERT by micro-SPECT/CT imaging, autoradiography and immunohistochemistry studies.
目錄
頁次
目錄…………………………………………………………………… Ⅰ
圖目錄………………………………………………………………… Ⅴ
附錄目錄……………………………………………………………… Ⅷ
中文摘要……………………………………………………………… Ⅸ
英文摘要……………………………………………………………… ⅩⅠ
第一章 緒論………………………………………………………… 1
第一節 血清素系統…………………………………………… 3
壹、血清素之合成機轉、接受器與功能…………………… 3
貳、血清素轉運體之位置、分佈與功能…………………… 8
參、血清素與血清素轉運體………………………………… 8
第二節 血清素轉運體之核子醫學造影新藥―[123I]ADAM… 9
壹、[123I]ADAM與血清素轉運體………………………....... 9
貳、[123I]ADAM在全身、腦部之生物分佈……………...…. 10
參、[123I]ADAM在神經精神疾患中之生物分佈……...…..... 12
第三節 利用SPECT觀察血清素轉運體之活體造影………... 12
壹、SPECT觀察正常人體中對血清素轉運體之造影...……. 12
貳、SPECT觀察精神性疾患中對血清素轉運體之造影...…. 14
參、SPECT觀察神經性疾患中對血清素轉運體之造影...…. 14
第四節 實驗目的………………………………………………. 16
第二章 材料與方法…………………………………………………. 17
第一節 實驗設計………………………………………………. 17
第二節 實驗材料………………………………………………. 18
壹、實驗動物………………………………………………. 18
貳、實驗用藥………………………………………………. 18
參、實驗器材………………………………………………. 19
第三節 放射性藥物[123I]ADAM之製備……………………… 19
第四節 大白鼠於微小型單光子放射電腦斷層攝影合併電腦斷層設備之活體腦部影像擷取與分析…………………. 20
壹、大白鼠造影模式之建立………………………………. 20
貳、[123I]ADAM於正常大白鼠腦部之造影及分佈情形… 21
參、抗憂鬱藥物-帕羅西汀(Paroxetine)於大白鼠腦部造影21
肆、5,7-DHT造成大白鼠縫核損傷模式之建立及造影…. 22
第五節 大白鼠腦部血清素轉運體之免疫組織化學染色……. 22
壹、組織固定………………………………………………. 22
貳、免疫組織化學染色……………………………………. 23
第六節 大白鼠腦部磁振造影切面解剖影像之擷取…………. 24
第七節 自動放射攝影及定量法………………………………. 25
第八節 [123I]ADAM之生物分佈……………………………… 26
第九節 資料分析與統計………………………………………. 26
第三章 實驗結果……………………………………………………. 27
第一節 微小型單光子放射電腦斷層合併電腦斷層造影…..... 27
壹、正常動物………………………………………………. 27
貳、給予不同劑量之抗憂鬱藥物─帕羅西汀(Paroxetine). 27
參、5,7-DHT造成縫核損傷之模式…….………………… 28
第二節 自動放射顯影……………………..…………………... 32
壹、正常動物………………………………………………. 32
貳、給予不同劑量之抗憂鬱藥物─帕羅西汀(Paroxetine). 34
參、5,7-DHT造成縫核損傷之模式….…………………… 34
第三節 免疫組織化學染色……………………………………. 39
壹、正常動物………………………………………………. 39
貳、5,7-DHT造成縫核損傷之模式…….………………… 41
第四節 磁振造影、微小型單光子放射電腦斷層攝影合併電腦斷層造影、自動放射顯影、以及免疫組織化學染色圖之矢狀及冠狀切面影像比較……………………………..... 46
壹、正常動物………………………………………………. 46
貳、時間活度曲線圖…………………………………….… 47
參、給予不同劑量之抗憂鬱藥物─帕羅西汀(Paroxetine). 48
肆、5,7-DHT造成縫核損傷之模式…….………………….48
第四章 討論………………………………………………………… 55
第一節 單光子放射電腦斷層攝影與正子斷層攝影之比較… 55
第二節 不同準直儀對造影結果之影響…………………….... 56
第三節 微小型單光子放射電腦斷層合併電腦斷層造影之缺點與限制………………………………………………… 56
第四節 利用微小型單光子放射電腦斷層合併電腦斷層造影、自.動放射顯影、以及免疫組織化學染色觀察大白鼠腦中血清素轉運體之結果比較……………………………… 57
第五章 結論………………………………………………………… 59
第六章 參考文獻…………………………………………………… 60
第七章 附錄………………………………………………………… 70
第六章 參考文獻

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