Synthesis and biological evaluation of novel (TcN)-Tc-99m-labeled bisnitroimidazole complexes containing monoamine-monoamide dithiol as potential tumor hypoxia markers
Synthesis and biological evaluation of novel (TcN)-Tc-99m-labeled bisnitroimidazole complexes containing monoamine-monoamide dithiol as potential tumor hypoxia markers
复制标题
新型（TcN）-Tc-99m标记双硝基咪唑复合物（含单胺-单酰胺二硫醇）作为潜在肿瘤缺氧标志物的合成和生物学评价
DOI：
10.1007/s10967-014-3235-6
复制
发表时间：
2014
影响因子：
1.6
通讯作者：
Chu Taiwei
中科院分区：
文献类型：
--
作者：
Mei Lei;Sun Wenjing;Chu Taiwei
肿瘤乏氧可导致放射损伤和化疗抵抗，从而降低临床治疗的效果，因此用放射性乏氧标记物检测肿瘤乏氧对肿瘤的控制具有重要意义。具有两个生物还原基团的放射性药物，如丙烯胺肟-双硝基咪唑或单胺-单酰胺二硫醇（MAMA）-双硝基咪唑，具有改善缺氧选择性的潜力。为了获得性能更好的放射性药物，我们合成了两种新型的双硝基咪唑和MAMA配体的[99 mTcN]2+肿瘤乏氧靶向配合物。并对其理化性质和生物分布进行了研究。两种配合物均具有良好的稳定性和亲水性。与不含硝基咪唑基团的对照复合物相比，它们显示出更快的血液和软组织清除、更好的肿瘤保留和有利的肿瘤-组织比。此外，这两种配合物均比相应的[99 mTcO]3+配合物具有更好的生物分布模式。这些结果表明，99 mTcN标记MAMA-双硝基咪唑配合物具有在体肿瘤乏氧显像的潜力。
Tumor hypoxia can decrease the efficacy of clinical therapy due to resistance toward radiation damage and chemotherapy, thus detection of tumor hypoxia by radiolabeled hypoxia markers is important for the control of tumor. Radiopharmaceuticals with two bioreductive groups, such as propylene amine oxime-bisnitroimidazole or monoamine-monoamide dithiol (MAMA) -bisnitroimidazole, have potential to improve hypoxia selectivity. In order to obtain radiopharmaceuticals with better features, we synthesized two novel [99mTcN]2+complexes with bisnitroimidazole moieties and MAMA ligand for targeting tumor hypoxia. Their physicochemical characters and biodistribution were also investigated. Both the [99mTcN]2+complexes show good stability and hydrophilicity. They show faster clearance from blood and soft tissues, better tumor retention and favorable tumor-to-tissue ratios compared with a control complex without nitroimidazole group. In addition, both of them show more favorable biodistribution patterns than the corresponding [99mTcO]3+complexes. These results indicate that the99mTcN-labeled MAMA-bisnitroimidazole complexes would have potential to image tumor hypoxia in vivo.