2013-01-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/645808摘要：研究目的: In-111/Tc-99m DTPA- hexa lactoside (HexLac) 是核研發展的特異標定在肝臟 細胞膜上的受體 Asialoglycoprotein receptors（ASGP-R）的藥劑,過去我們 以土撥鼠自然感染土撥鼠肝炎病毒(WHV)的模型已經顯示 HexLac 的攝取 和肝炎感染後肝臟產生纖維化或硬化程度呈負相關性, 我們也發現在肝細胞 癌病灶的攝取量更低. 另外 Tc-99m galactosy human serum albumin (GSA) 是 國外已上市的 ASGP-R 藥物, 但是一直尚未見到有大規模臨床運用. 本研究 計劃評估:1. 比較 In-111/Tc-99m HexLac 及 Tc-99m GSA 在土撥鼠自然感染肝炎病毒 的模型的攝取差異2. 找出 In-111/Tc-99m HexLac 較 Tc-99m GSA的優勢, 為進一步臨床試驗之 準備與實證研究方法: 以臨床用的 SPECT/CT gamma camera 在分別在無肝炎病毒感染、有肝炎病 毒感染及有肝炎病毒感染且已形成肝癌病灶的土撥鼠, 每隻土撥鼠進行Tc-99m GSA 及 In-111/Tc-99m HexLac 動態及斷層面造影, 定量其在各重要 器官的分佈、肝臟攝取速率、liver/blood pool ratio、及 Specific ASGP-R binding potential 等, 並比較兩種藥物的特異性 binding.預期成果: 找出 In-111/Tc-99m HexLac 相較 Tc-99m GSA在評估存活肝細胞及殘留肝功 能的優勢, 做為即將進行的臨床試驗之實證。<br> Abstract: PURPOSE: In-111/Tc-99m DTPA-hexa lactoside (HexLac) is an asialoglycoprotein receptor (ASGP-R) targeting agent developed by Institute of Nuclear Energy Research (INER). We have demonstrated that it is a highly specific ASGP-R targeting agent which reflect the viability of hepatocytes. The tracer uptake is significantly correlated with the hepatic function reserve. We also notice that hepatoma is HexLac non or low-avid. In the meanwhile, Tc-99m galactosy human serum albumin (GSA) is a commercial ASGP-R agent since 2000. Up to now, its clinical usefulness is still very limited. The objectives of this study are to: (1) compare the uptake difference between In-111/Tc-99m HexLac and Tc-99m GSA using the woodchuck hepatitis B virus (WHV)-infected model, and (2) find out the advantages of In-111/Tc -99m HexLac overTc-99m GSA.METHODS:1. Animals: 2 healthy, 2 chronic woodchuck hepatitis B virus (WHV)-infected and 2 HCC–bearing woodchucks,2. Imaging: Using a commercial SPEC/CT (Symbia T2, Siemens Healthcare) equipped with medium energy collimators, dynamic and SPECT imaging will be performed after injection of ASGP-R tracers (HexLac and GSA)3. Data analysis:a. For dynamic study, the regions of interest will be drawn on the heart and liver and total count/sec for each ROI will be recorded.b. For SPECT images, the average radioactivity count for liver, heart, kidneys, urinary bladder will be obtained by placing the region of interest (ROI) inside the corresponding organs . Specific ASGP-R binding potential will be calculated for each woodchuck by the equation: (Mean count ROI (liver)- Mean count ROI (heart))/Mean count ROI (heart). The specific binding potentials of Tc-99m GSA and In-111/Tc-99m HexLacwill be compared.肝細胞膜受體In-111/Tc-99m DTPA-hexa lactoside (HexLac)Tc-99m galactosy human serum albumin(GSA)肝炎肝硬化肝癌土撥鼠模型asialoglycoprotein receptor (ASGP-R)In-111/Tc-99m DTPA-hexa lactoside (HexLac)Tc-99m galactosy human serum albumin (GSA)hepatitisliver cirrhosishepatomawoodchuck model