Species dependence of [64Cu]Cu-Bis(thiosemicarbazone) radiopharmaceutical binding to serum albumins
Species dependence of [64Cu]Cu-Bis(thiosemicarbazone) radiopharmaceutical binding to serum albumins
复制标题
DOI：
10.1016/j.nucmedbio.2007.11.009
复制
发表时间：
2008-04-01
影响因子：
3.1
通讯作者：
Green, Mark A.
中科院分区：
文献类型：
--
作者：
Basken, Nathan E.;Mathias, Carla J.;Green, Mark A.
简介：三种铜（II）的相互作用（缩氨基硫脲）正电子发射断层扫描放射性药物与人血清白蛋白和另外四种哺乳动物的血清白蛋白进行了评价。Cu-64标记双乙酰双（N-4-甲基氨基硫脲基）铜（II）（Cu-ATSM），双异戊醛（N-4-甲基氨基硫脲基）铜（II）（Cu-PTSM）和乙基乙二醛双（氨基硫脲基）铜（II）（Cu-ETS）的合成和其结合的人，犬，大鼠，狒狒和猪血清白蛋白通过超滤定量。蛋白质结合也测定了每个示踪剂在人，猪，大鼠和小鼠serum.Results：这些中性，亲脂性铜螯合物与血清白蛋白的相互作用是高度化合物和物种依赖性。Cu-PTSM和Cu-ATSM对人血清白蛋白（HSA）表现出特别高的亲和力，而Cu-ETS的白蛋白结合对物种相对不敏感。在HSA浓度为40 mg/ml时，“游离%”Cu-PTSM、Cu-ATSM和Cu-ETS的放射性药物（非白蛋白结合）水平分别为4.0 +/-0.1%、5.3 +/- 0.2%和38.6 +/- 0.8%。物种-当使用动物模型预测放射性药物的分布和动力学时，可能需要考虑放射性药物与血清白蛋白结合的依赖性变化。这些化合物在人体内。(C)2008年爱思唯尔公司All rights reserved.
Introduction: Interactions of three copper(II) bis(thiosemicarbazone) positron emission tomography radiopharmaceuticals with human serum albumin, and the serum albumins of four additional mammalian species, were evaluated.Methods : Cu-64-labeled diacetyl bis(N-4-methylthiosemicarbazonato)copper(II) (Cu-ATSM), pyruvaldehyde bis(N-4-methylthiosemicarbazonato)copper(II) (Cu-PTSM) and ethylglyoxal bis(thiosemicarbazonato)copper(II) (Cu-ETS) were synthesized and their binding to human, canine, rat, baboon and porcine serum albumins quantified by ultrafiltration. Protein binding was also measured for each tracer in human, porcine, rat and mouse serum.Results: The interaction of these neutral, lipophilic copper chelates with serum albumin is highly compound- and species-dependent. Cu-PTSM and Cu-ATSM exhibit particularly high affinity for human serum albumin (HSA), while the albumin binding of Cu-ETS is relatively insensitive to species. At HSA concentrations of 40 mg/ml, "% free" (non-albumin-bound) levels of radiopharmaceutical were 4.0 +/- 0.1%, 5.3 +/- 0.2% and 38.6 +/- 0.8% for Cu-PTSM, Cu-ATSM and Cu-ETS, respectively.Conclusions: Species-dependent variations in radiopharmaceutical binding to serum albumin may need to be considered when using animal models to predict the distribution and kinetics of these compounds in humans. (C) 2008 Elsevier Inc. All rights reserved.