Synthesis and biodistribution of novel 99mTc-nitrido methylpiperidine dithioformate derivatives as potential brain imaging agents
Synthesis and biodistribution of novel 99mTc-nitrido methylpiperidine dithioformate derivatives as potential brain imaging agents
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作为潜在脑成像剂的新型 99mTc-硝基甲基哌啶二硫代甲酸酯衍生物的合成和生物分布
DOI：
10.1002/jlcr.1587
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发表时间：
2009-05-15
影响因子：
1.8
通讯作者：
Wang, Xuebin
中科院分区：
文献类型：
--
作者：
Lu, Jie;Xu, Mingyan;Wang, Xuebin
合成了3个在哌啶环上被甲基取代的二硫甲酸配体：1-（2-甲基哌啶-1-基）-二硫甲酸钾（2-mp）、1-（3-甲基哌啶-1-基）-二硫甲酸钾（3-mp）和1-（4-甲基哌啶-1-基）-二硫甲酸钾（4-mp）。以[(TcN)-Tc-99m](int)（2+）中间体为原料，以高收率（>95%）制备了相应的Tc-99m-nitrido配合物，并通过薄层色谱和高效液相色谱进行了表征。所有中性99mTc-nitrido络合物在生理条件下均稳定且亲脂，log P值在1.40 ~ 1.58之间。体内生物分布结果表明，所有99mTc-nitrido复合物均表现出高脑吸收和长滞留时间。其中，(TcN)-Tc-99m-4mp表现出最佳的脑成像性能，在5、30、60和120 min时脑摄取分别为3.40+/-0.24、3.22+/-0.31、2.72+/-0.28和2.22+/-0.18% ID/g。此外，利用Gaussian 03程序包，采用B3LYP/6-31G*（LANL2DZ为Tc）方法，研究了哌啶环上邻位、间位和对位甲基取代的99mTcN配合物的立体化学对生物分布性能的影响。
Three dithioformate ligands with methyl substituted on the piperidine rings, potassium 1-(2-methylpiperidine-1-yl)-dithioformate (2-mp), potassium 1-(3-methylpiperidine-1-yl)-dithioformate (3-mp) and potassium 1-(4-methylpiperidine-1-yl)-dithioformate (4-mp) were synthesized. The corresponding Tc-99m-nitrido complexes were prepared in high yield (>95%) through the [(TcN)-Tc-99m](int)(2+) intermediate and characterized by thin layer chromatography and high-performance liquid chromatography. All the neutral 99mTc-nitrido complexes were stable under physiological conditions and lipophilic with log P values between 1.40 and 1.58. In vivo biodistribution results showed that all the 99mTc-nitrido complexes displayed high brain uptakes and long retention times. Among them, (TcN)-Tc-99m-4mp, demonstrated the best properties for brain imaging with the brain uptake 3.40+/-0.24, 3.22+/-0.31, 2.72+/-0.28 and 2.22+/-0.18% ID/g at 5, 30, 60 and 120 min p.i., respectively. Moreover, the influence of stereochemistry of the 99mTcN complexes with methyl substitution on ortho, meta and para positions on piperidine ring on the biodistribution properties were investigated with B3LYP/6-31G*(LANL2DZ for Tc) method using the Gaussian 03 program package.