鎝氧環丁基丙烯氨圬非鏡像立體異構物作為局部腦血流腦灌注造影劑之動物實驗評估
蔡長書1 葉錫溶2
1慈濟技術學院放射技術系 2國立清華大學原子科學系
摘 要
在核子醫學應用方面，99m Tc0-d，1-CB-PA0與99m Tc0-meso-CB-PA0兩者皆具有高電中性及高親脂性。而其放射化學純度分別為94.5±0.6 ﹪及96.6±1.2 ﹪；且具高體外穩定性，在 6小時以內分解比率小於 5﹪。在老鼠生物分佈實驗方面，99m Tc0-d，1-CB-PA0與99m Tc0-meso-CB-PA0在 5，30，60分鐘的腦部攝取量分別為0.78﹪，0.96﹪，0.84﹪inj. dose；以及0.76﹪，0.77﹪，0.78﹪inj. dose。在兔子之腦部造影實驗中，證實兩者皆可穿透血腦障壁，且在 4小時以內分佈穩定，滯留時間亦足夠單光子釋出電腦斷層造影，但meso-form 之腦部對全部活性之百分比遞減速率較快。 根據本實驗之結果及文獻之比較可獲知，99m Tc0-d，1-CB-PA0具有以下之優點：1.可獲致高產率、高立體化學純度之配位子。2.鎝錯合物具有高電中性、高親脂性、分子量小500 道耳吞。3.具有比現在醫院臨床使用之99m Tc-d，1-HM-PA0較好之體外穩定性。4.初步動物實驗之品質良好，媲美商用99m Tc-d，1-HM-PA0。可作為一極具潛力之局部腦血流腦灌注造影劑。
關鍵字：環丁基丙烯氨圬非鏡像立體異構物，親脂性，放射化學純度，血腦障壁，單光子釋出電腦斷層造影。
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Animal Tests of 99mTcO-CB-PAO Diastereoisomers As a potential Brain Perfusion Imaging Agent For Evaluation of Regional Cerebral Blood Flow
Chang-Shu Tsai 1 Si-Jung Yeh 2
1 Department of Radiological Technology Tzu-Chi College of Technology
2 Department of Atomic Science National Tsing Hua University
Abstract
For the application in the field of nuclear medicine both 99m TcO-d,1-CB-PAO and 99m TcO-meso -CB-PAO are electrically neutral, and highly lipophilic. The radiochemical purities were 94.5±0.6%及96.6±1.2%, respectively. Their in-vitro stabilities were very high ( < 5 % decomposed within 6 hrs ). Biological distribution in rats were also studied. For 99m TcO-d,1-CB-PAO, the amount retained in the brain after 5, 30, 60 min. sacrifice were 0.78, 0.96, 0.84% inj. dose. and those for 99m TcO-meso -CB-PAO were 0.76, 0.77, 0.78% inj. dose, respectively. The study in brain imaging using rabbits showed the evidences that both d, 1 and meso isomers passed through blood-brain barrier (BBB), and stayed for 4 hrs without redistribution in the brain. This duration is actually good enough for single photon emission computed tomography (SPECT) imaging. However, it must be pointed out that for meso-form, the wash-out speed is too fast to be practical. Based on the comparision on the experimental results shown in this work with those found in the literatures, one notices that the following advantages are with our in-house 99m TcO-d, 1-CB-PAO: 1.Concerning the preparation of ligand better yield and high purity were obtained. 2.The complex was found high lipophilic, electrically neutral, molecular weight < 500 Dalton. 3.Better in-vitro stability was observed compared to commerical 99m TcO-d, 1-HM-PAO now in clinical use. 4.Preliminary experiment on animals showed that the quality of image in the brain was as good as that of commercial 99m TcO-d, 1-HM-PAO. In conclusion, 99m TcO-d, 1-CB-PAO may be a potential brain perfusion imaging agent for evaluation of regional cerebral blood flow (rCBF).
Keywords : 99m TcO-CB-PAO diastereoismers, lipophilicity, radiochemical purity, blood-brain barrier, SPECT