A novel ternary ligand system useful for preparation of cationic 99mTc-diazenido complexes and 99mTc-labeling of small biomolecules
A novel ternary ligand system useful for preparation of cationic 99mTc-diazenido complexes and 99mTc-labeling of small biomolecules
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DOI：
10.1021/bc0502715
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发表时间：
2006-03-01
影响因子：
4.7
通讯作者：
Liu, S
中科院分区：
文献类型：
--
作者：
Kim, YS;He, ZJ;Liu, S
该报告描述了一种由苯肼、含冠醚的二硫代氨基甲酸酯（DTC）和PNP型双膦（PNP）组成的新型三元配体系统。三种不同配体与 Te-99m 的组合产生阳离子 Tc-99m-二氮烯基复合物，[Tc-99m(NNAr)(DTC)(PNP)](+)，具有用于心脏成像的潜在放射性药物。阳离子 Tc-99m-二氮烯基配合物的合成可以分两步完成。例如，苯肼与 (TcO4-)-Tc-99m 在过量氯化亚锡和 1,2-二氨基丙烷-N,N,N',N'-四乙酸 (PDTA) 存在下在 100 摄氏度下反应，生成 [Tc-99m(NNPh)(PDTA)(n)] 中间体，然后与钠反应N-(二硫代氨基甲酸酯)-2-氨基甲基-15-Crown-5 (L4) 和 N,N-双[2-(双(3-乙氧基丙基)膦基)乙基]乙氧基乙胺 (PNP6) 在 100°C 下反应 15 分钟，以高产率 (> 90%) 得到络合物 [Tc-99m(NNPh)(L4)(PNP6)](+)。阳离子配合物 [Tc-99m(NNPh)(DTC)(PNP)](+) 在 >= 6 It 内稳定。使用示踪剂 (99mTc) 水平的混合配体实验确定其组成为 1:1:1:1（Tc:NNPh:DTC:PNP），并通过模型化合物 [Re(NNPh)(L4)(L6)](+) 的 ESI-MS 光谱数据进一步证实。研究发现，DTC 和双膦对其阳离子 Tc-99m-二氮烯基配合物的亲脂性有显着影响。 Tc-99m 标记效率实验的结果表明，4-肼基苯甲酸 (HYBA) 可用作小生物分子 Tc-99m 标记的双功能偶联剂。然而，HYBA 的 99'Tc 标记效率远低于以三甲基甘氨酸和三苯基膦-3,3',3"-三磺酸三钠 (TPPTS) 作为共配体的 6-肼烟酸 (HYNIC)。
This report describes a novel ternary ligand system composed of a phenylhydrazine, a crown ether-containing dithiocarbamate (DTC), and a PNP-type bisphosphine (PNP). The combination of three different ligands with Te-99m results in cationic Tc-99m-diazenido complexes, [Tc-99m(NNAr)(DTC)(PNP)](+), with potential radiopharmaceuticals for heart imaging. Synthesis of cationic Tc-99m-diazenido complexes can be accomplished in two steps. For example, the reaction of phenylhydrazine with (TcO4-)-Tc-99m at 100 degrees C in the presence of excess stannous chloride and 1,2-diaminopropane-N,N,N',N'-tetraacetic acid (PDTA) results in the [Tc-99m(NNPh)(PDTA)(n)] intermediate, which then reacts with sodium N-(dithiocarbamato)-2-aminomethyl-15-Crown-5 (L4) and N,N-bis[2-(bis(3-ethoxypropyl)phosphino)ethyl]ethoxyethylamine (PNP6) at 100 degrees C for 15 min to give the complex, [Tc-99m(NNPh)(L4)(PNP6)](+) in high yield (> 90%). Cationic complexes [Tc-99m(NNPh)(DTC)(PNP)](+) are stable for >= 6 It. Their composition was determined to be 1:1:1:1 for Tc:NNPh:DTC:PNP using the mixed-ligand experiments on the tracer (99mTc) level and was further confirmed by the ESI-MS spectral data of a model compound [Re(NNPh)(L4)(L6)](+). It was found that both DTCs and bisphosphines have a significant impact on the lipophilicity of their cationic Tc-99m-diazenido complexes. Results from a Tc-99m-labeling efficiency experiment showed that 4-hydrazinobenzoic acid (HYBA) might be useful as a bifunctional coupling agent for Tc-99m-labeling of small biomolecules. However, the 99'Tc-labeling efficiency of HYBA is much lower than that of 6-hydrazinonicotinic acid (HYNIC) with tricine and trisodium triphenylphosphine-3,3',3"-trisulfonate (TPPTS) as coligands.