Abstract
本研究的主要目的是探討半胱胺酸鎝錯化合物的生物分布，進而評估其取 代傳統核醫腎臟造影劑之可行性。研究過程主要是比較半胱胺酸鎝錯化合 物(Tc-99m-cysteine complex)與傳統的腎臟造影劑 I-131 OIH(o- iodohippurate)和新上市的藥劑Tc-99m-MAG3 (mercaptoacetyltriglycine)的相似性，研究方法包括：Tc-99m- cysteine complex、Tc-99m-MAG3和I-131 OIH生物體的活性分布、血液中 的清除率與運輸機制、排泄速率的研究以及使用抑制劑2,4- dinitrophenol或probenecid進行排泄機制的探討；最後利用實際的活體 照影，評估Tc-99m-cysteine complex作為腎臟造影劑的可行性。從實驗 結果得知Tc-99m-cysteine complex、Tc-99m-MAG3和I- 131 OIH的靶的器 官均為腎臟，且在血液中的清除率非常快，在注射後 1小時左右約有83% 的活性會由腎臟排泄，同時此三種核醫藥劑的排泄過程會受到腎小管分泌 脢抑制劑(2,4-dinitrphenol或probenecid)的抑制，因此可證實Tc-99m- cysteine complex類似於Tc-99m-MAG3和 I-131 OIH是經由腎小管分泌作 用排出體外。經由高效率凝膠層析法和SDS-PAGE(polyacrylamide gel electrophoresis)電泳法分析血漿證實，它們主要是與血漿白蛋白結合而 後運送到腎臟排出體外。且它們在代謝過程中，是以未經過分解的原型由 尿液中排出。將Tc-99m- cysteine complex與目前使用的腎臟造影劑比較 ，可發現其生物分布特性類似於Tc-99m-MAG3或I-131 OIH。從活體照影結 果可直接證實 Tc-99m-cysteine complex適合作腎臟動態照影之藥劑。綜 合本研究的結果可發現Tc-99m-cysteine complex確實有成為新核醫腎臟 造影劑的潛力。 The aim of this research is to compare the biological behavior of Tc-99m cysteine complex with I-131 OIH ( o- iodohippurate) and Tc-99m MAG3 (mercaptoacetyltriglycine), then evaluate the probability of Tc-99m cysteine complex as a renal imaging agent. Several experiments were explored to evaluate the biological characteristics, namely, the target organ in the biodistribution, blood clearance of these complexes, the transport and excretion mechanism, and the renal excretion pattern in the presence and absence of tubular transport inhibitor(2,4-dinitrophenol, probenecid). Finally, the in vivo image was carried out to evaluate the possibility of Tc-99m cysteine complex as a renal imaging agent. It reveals that kidneys are the target organ and the serum albumin serves as a carrier for the transport of these agents to the kidneys. The blood clearance of these radiopharmaceuticals is very fast, about 83% of injected activity is excreted from the kidneys at 1 hour postinjection. The renal transport inhibitor, indeed, depressed the excretory rate of Tc-99m cysteine, Tc-99m MAG3 and I-131 OIH, it can suggest that all of these agents were excreted by renal tubular secretion and were excreted without any dissociation during the metabolic process. From the result of in vivo renal image, Tc-99m cysteine is a remarkable renal dynamic imaging agent. Thus, it has potential to be a new renal imaging radiopharmaceutical.