2017-01-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/711114摘要：肝臟是人體攝取代謝結合排泄各種體內產生或由體外吸收而來的物質的最重要器官。當肝臟功能殘餘降低至一個閥值就可能發生肝臟衰竭。因此，正確評估殘留肝臟功能對於預測病程及決定臨床治療方向非常重要。目前在臨床上靜態測量肝臟血清酵素等指數或動態測量以indocyanine green (ICG)clearance test 來做肝功能的評估，但這些測量和臨床及病理常有不合的發現，和病人預後相關性也較低。 因此，臨床上急需發展準確的藥物及影像檢查來精確評估並定量肝功能。目前核研所已發展Asialoglycoprotein (ASGP) 受體 (ASGP-R) 的縮胺酸藥物 (HexavalentLactoside, HL),以In-111 標誌的 In-111 HL 可以正確定量正常肝細胞表面ASGP-R。這個受體的數量已被證明和殘留肝臟細胞及肝功能有極大得相關性。但是In-111 有以下限制性: 普及度差, 半衰期長,radiation exposure 大, 單光子造影的解析度低, 單光子造影較難做正確的定量分析等。目前核能研究所已發展出可用gallium-68 標誌的肝受體造影凍晶製劑(INER-038, Institute Nuclear EnergyResearch, Taoyuan, Taiwan). Ga-68 是正子衰變核種, 半衰期為 67.7 分鐘。以正子造影解析度高。本計畫預計發展出以Ga-68 標誌的ASGP-R 正子探針 (核研多蕾克鎵肝功能造影劑, INER-038,Institute Nuclear Energy Research, Taoyuan, Taiwan), 以小豬動物模型, 經由正子動態造影建立該藥物的藥動學, 生物分佈, 輻射劑量及安全性, 並確定定量肝臟切除後及肝衰竭的殘留肝功能的正確性, 做為未來該藥物進入人體臨床試驗的參考。<br> Abstract: liver is a critical organ which performs synthetic and secretory functions of endogenous andexogenous substances. When liver function deteriorates to a threshold limit, hepatic failure mayoccur. Therefore, accurate hepatic function determination is important for prognosis estimation andtherapy planning for patients with liver diseases. At present, static tests using various laboratoryparameters and dynamic test using indocyanine green (ICG) clearance are two major methods.However, these two kinds of methods were reported to be inconsistent with clinical manifestations,pathological finding and prognosis sometimes. To develop a more precise tool of liver functionreserve evaluation is warranted.At present, INER developed a peptide (Hexavalent Lactoside, HL) which targets to theAsialoglycoprotein (ASGP) receptors (ASGP-R) on hepatic cell membrane. It was labeled by In-111previously and has been reported that the imaging tool appeared to be a good, specific visual andquantitative predictor of functional liver reserve. However, there are some limitations, such as thepoor availability, long half-life and high radiation exposure of In-111, low spatial resolution of SPECTimaging, and lack the ability of quantitative analysis. Recently, INER has developed a lyophilized kitfor Ga-68 labeling (INER-038, Institute Nuclear Energy Research, Taoyuan, Taiwan). Ga-68 is apositron decay radionuclide with half-life of 67.7 min. The resolution of PET imaging is muchimproved compared with that of SPECT imaging.The objectives of this study are: (1) develop standardized labeling, quality control, and PETimaging protocol of Ga-68 NOTA-HL PET probe for ASGP-R, (2) using porcine model to establishthe pharmacokinetics, bio-distribution, dosimetry and safety of INER-038 (Institute Nuclear EnergyResearch, Taoyuan, Taiwan), (3) quantification and diagnostic accuracy of Ga-68 NOTA-HL PET.The data can be used as references for clinical trial in the near future.Ga-68肝功能Asialoglycoprotein 受體正子造影小豬動物模型Ga-68liver function reserveAsialoglycoprotein receptorpositron emission tomographyporcine model