臺灣博碩士論文加值系統

　　18F-AV-133為偵測VMAT2之嶄新核醫藥物，藉以評估帕金森氏病人多巴胺神經元退化情形，與目前臨床常用的DAT造影之藥物－99mTc-TRODAT比較，18F-AV-133有高解析度、敏感度、不易受治療藥物影響之優點，具臨床應用潛力。而在廣泛運用於臨床前，須針對18F-AV-133於帕金森氏病之鑑別力，找出最佳造影流程與影像的定量分析。本論文將研究18F-AV-133之最佳造影時間，並與99mTc-TRODAT比較其診斷效力。以4位健康受測者與9位帕金森氏病人影像，利用定量與半定量分析法，分別計算SUVR與DVR，探討二參數相關性以及18F-AV-133之SUVR影像與健康對照組與帕金森氏病人間的鑑別力，綜合評估最佳造影時間。獲得最佳造影時間之影像後，評估18F-AV-133影像與臨床資料的相關性，並與99mTc-TRODAT影像比較。
　　結果中發現，於90-100分鐘，SUVR與DVR有高度相關，且SUVR影像於健康對照組與帕金森氏病病人間有高鑑別力，因此推估90-100分鐘為最佳造影時間。18F-AV-133影像在區別帕金森氏病與健康對照組之能力優於99mTc-TRODAT影像，且與臨床資料之相關性也與DAT影像類似。因此，18F-AV-133有潛力成為比99mTc-TRODAT更具臨床診斷價值之核醫藥物，以利早期發現與早期診斷帕金森氏病。

18F-AV-133 is a novel PET tracer for imaging the vesicular monoamine transporter 2 (VMAT2) in dopaminergic neuron degeneration of Parkinson diseases (PD) and is expected with more diagnosis power as compared to conventional SPECT tracer for DAT（dopamine transporter, DAT） imaging including 99mTc-TRODAT. Before the wide application in clinical trials, the optimization of scanning protocol and data quantitation for 18F-AV-133 is necessary to guarantee optimal diagnosis power in differentiation of PD from normal controls. This thesis is aimed to study the optimal scanning time, as well as compare the diagnosis power with that of 99mTc-TRODAT. The study included 4 normal controls (NCs) and 9 Parkinson diseases patients. The imaging time window was optimized by using a simple semi-quantitative SUVR (standardized uptake value ratio) and its correlation to a quantitative analysis from DVR (distribution volume ratio), as well as discriminating capability of PD from NCs. After ideal time window was obtained, 18F-AV-133 PET images were correlated with clinical data, and compare to 99mTc-TRODAT SPECT images in same subjects.
As the results indicated, at 90-100 min time window, SUVRs were strongly correlated with DVR, and showed good differentiation between NCs and PD patients. Therefore, 90-100 min was considered as the optimal time window. 18F-AV-133 imaging showed better discrimination between NCs and PD patients, and better correlation with clinical characteristics than 99mTc-TRODAT imaging. In these regards, 18F-AV-133 PET is promising for clinical use of detecting monoaminergic terminal reduction in PD patients.

目錄
誌謝 iv
中文摘要 v
英文摘要 vi
目錄 viii
表目錄 xi
圖目錄 xii
第一章 簡介 1
1-1　關於帕金森氏病 1
1-1-1　帕金森氏病臨床表現與診斷 2
1-1-2　帕金森氏病致病原因 8
1-2　帕金森氏病之核醫造影 10
1-3 實驗目的 15
第二章 定量與半定量分析 16
2-1　定量分析 17
2-1-1　隔室模型（compartment model） 17
2-1-2　參考組織模型（reference tissue model） 23
2-2　半定量分析 24
2-3　Logan graphical model之DVR與SUVR關係 26
第三章 實驗材料與方法 28
3-1　18F-AV-133的製備 28
3-2　受試者與來源(Subjects) 28
3-3　造影流程（Imaging studies） 29
3-4　感興趣體積(VOI)的定義 30
3-5　評估18F-AV-133最佳造影時間 32
3-5-2　最佳造影時間評估 33
3-6　比較18F-AV-133與99mTc-TRODAT於健康對照組與帕金森氏病病人之造影 36
3-6-1　影像分析 36
3-6-2　臨床診斷資料分別與18F-AV-133正子造影和99mTc-TRODAT單光子斷層掃描造影之影像相關性分析 36
第四章 實驗結果 39
4-1　評估18F-AV-133最佳造影時間 40
4-1-1　18F-AV-133 SUVR與DVRLogan、DVR2C4k的相關性 41
4-1-2　SUVR於健康受測者與帕金森氏病病人間的區別力 47
4-2　比較18F-AV-133與99mTc-TRODAT於健康對照組與帕金森氏病病人之
造影 52
4-2-1　18F-AV-133 SUVR與99mTc-TRODAT UR之相關性 53
4-2-2　99mTc-TRODAT單光子斷層掃描與臨床診斷資料之相關性 55
4-2-3　18F-AV-133正子造影與臨床診斷資料相關性 58
第五章 討論與結論 61
5-1　評估18F-AV-133最佳造影時間之討論 61
5-2　比較18F-AV-133與99mTc-TRODAT於健康對照組與帕金森氏病病人之造影之討論 66
5-3 結論 70
5-4 未來發展重點 71
參考文獻 72















表目錄
表1-1　Unified Parkinson Disease Rating Scale－Part Ⅰ、Part Ⅱ 4
表1-2　Unified Parkinson Disease Rating Scale－Part Ⅲ 5
表1-3　Unified Parkinson Disease Rating Scale－Part Ⅳ 6
表1-4　Hoehn and Yahr stage 7
表3-1　Clinical Laterality Score 29
表4-1　受試者之臨床表徵 39
表4-2　18F-AV-133於8個VOI的DVR2C4k與DVRLogan 48
表4-3　NC與PD於各VOI的18F-AV-133 SUVR與99mTc-TRODAT UR 54
表4-4　18F-AV-133 SUVR與99mTc-TRODAT UR於病徵側有效差異值 55















圖目錄
圖1-1　多巴胺直接與間接神經傳導路徑示意圖 9
圖1-2 多巴胺神經傳導系統，各核醫藥物做用位置示意圖 12
圖2-1　雙隔室模型示意圖 19
圖2-2　三隔室模型示意圖 21
圖3-1　本研究所用的8個VOI與參考組織 32
圖4-1　18F-AV-133健康受測者與帕金森氏病病人的動態造影 40
圖4-2　 13位受測者8個VOI的DVRLogan與DVR2C4k之線性相關 41
圖4-3　 13位受測者8個VOI的SUVR與DVR2C4k、DVRLogan於10-20分鐘、20-30分鐘、50-60分鐘之線性相關 42
圖4-4　 13位受測者8個VOI的SUVR與DVR2C4k、DVRLogan於60-70分鐘、70-80分鐘、80-90分鐘之線性相關 43
圖4-5　 13位受測者8個VOI的SUVR與DVR2C4k、DVRLogan於90-100分鐘、100-110分鐘、110-120分鐘之線性相關 44
圖4-6　 13位受測者8個VOI的SUVR與DVR2C4k、DVRLogan於120-130分鐘、130-140分鐘、160-170分鐘之線性相關 45
圖4-7　14個時間區間SUVR分別與DVR2C4k、DVRLogan的線性回歸結果 46
圖4-8 健康對照組與帕金森氏病病人於病徵側的尾核與外核的SUVR與時間關係曲線 49
圖4-9　14個時間區間，帕金森氏病病人在病徵側之於健康對照組時間與Mann-Whitney U test之p-value關係圖 49
圖4-10　尾核與外核於病徵側14個時間區間SUVR有效差異值結果 51
圖4-11　健康受測者與帕金森氏病病人T1 MRI、18F-AV-133注射後90-100分鐘SUVR之影像與99mTc-TRODAT打藥後4-5小時的UR影像 52
圖4-12　以散佈圖表示13位受測者6個VOI的18F-AV-133 SUVR與99mTc-TRODAT UR之相關性分析 53
圖4-13　99mTc-TRODAT UR於尾核與外核在影像上的病徵側與H-Y stage之相關性分析結果 56
圖4-14　尾核與外核99mTc-TRODAT影像上攝取值的對稱性與臨床症狀上的單側性等級之相關性 56
圖4-15　病徵側之尾核與外核99mTc-TRODAT UR與UPDRS總分、UPDRSm、UPDRS運動部分中的肢體僵硬與動作緩慢程度的分數之相關性 57
圖4-16　18F-AV-133 SUVR於尾核與外核在影像上的病徵側與H-Y stage之相關性分析結果 58
圖4-17　尾核與外核18F-AV-133正子造影攝取值的對稱性與臨床症狀上的單側性等級之相關性 59
圖4-18　病徵側之尾核與外核18F-AV-133 SUVR與UPDRS總分、UPDRSm、UPDRS運動部分中的肢體僵硬與動作緩慢程度的分數之相關性 60

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