一种用于99mTc标记蛋白质的新型双功能螯合剂的合成与评价：对羧乙基苯乙二醛 - 二（N - 甲基硫代半卡巴腙）

Synthesis and evaluation of a new bifunctional chelating agent for 99mTc labeling proteins: p-carboxyethylphenylglyoxal-di(N-methylthiosemicarbazone).

作者信息

Arano Y, Yokoyama A, Magata Y, Saji H, Horiuchi K, Torizuka K

出版信息

Int J Nucl Med Biol. 1986;12(6):425-30. doi: 10.1016/s0047-0740(86)80003-1.

Abstract

A new bifunctional chelating agent, p-carboxyethylphenylglyoxal-di(N-methylthiosemicarbazone) (CE-DTS), containing a di(N-methylthiosemicarbazone) as the technetium coordinating site and an aralkyl carboxylate site for the protein conjugation was synthesized. Coupling to human serum albumin (HSA), selected as a model protein was carried out by the phosphorylazide method using diphenylphosphoryl azide (DPPA). The conjugation level of CE-DTS to HSA played a critical role in its biological evaluation. A 99mTc-CE-DTS-HSA with high in vivo stability was obtained when CE-DTS was coupled to HSA at 1:1 molar ratio. This compound showed similar in vivo stability to 131I labeled HSA in mice and rabbits.

摘要

合成了一种新型双功能螯合剂对羧乙基苯乙二醛-二（N-甲基硫代半卡巴腙）（CE-DTS），它含有二（N-甲基硫代半卡巴腙）作为锝配位位点以及用于蛋白质偶联的芳烷基羧酸盐位点。选用人血清白蛋白（HSA）作为模型蛋白，通过使用二苯基磷酰叠氮化物（DPPA）的磷酰叠氮化物方法进行与CE-DTS的偶联。CE-DTS与HSA的偶联水平在其生物学评价中起着关键作用。当CE-DTS以1:1摩尔比与HSA偶联时，得到了具有高体内稳定性的99mTc-CE-DTS-HSA。该化合物在小鼠和兔子体内显示出与131I标记的HSA相似的体内稳定性。