Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, PR China.
Eur J Med Chem. 2012 Dec;58:50-63. doi: 10.1016/j.ejmech.2012.09.042. Epub 2012 Oct 4.
Four monoamine-monoamide dithiol (MAMA) ligands containing two or one nitroimidazole moieties were synthesized and labeled with (99m)Tc (labeling yield > 95%). The proposed structures of (99m)Tc-complexes are identified by comparison with analogous Re-MAMA complexes. (99m)Tc-MAMA complexes show better physicochemical characters than (99m)TcO-(PnAO-1-(2-nitroimidazole)). Reduction potentials of nitro groups of the rhenium complexes are within the range for bioreductive compounds. As expected, biodistribution studies demonstrate that the 2-nitroimidazole complex shows better tumor-to-tissue ratios than 4-nitroimidazole analog for mononitroimidazole complexes, but not for MAMA-bisnitroimidazoles due to higher lipophilicity. Both the bisnitroimidazole compounds show rapider excretion, lower background activity in liver and higher tumor-to-tissue ratios than the mononitroimidazoles. Better biodistribution characteristic makes both the MAMA-bisnitroimidazole complexes, especially (99m)Tc-15, be potential tumor hypoxia marker.
四种含有两个或一个硝基咪唑部分的单胺-单酰胺二硫醇（MAMA）配体被合成并用（99m）Tc 标记（标记产率>95%）。（99m）Tc-配合物的结构通过与类似的 Re-MAMA 配合物进行比较来确定。（99m）Tc-MAMA 配合物比（99m）TcO-（PnAO-1-（2-硝基咪唑））具有更好的物理化学性质。铼配合物中硝基的还原电位在生物还原化合物的范围内。正如预期的那样，生物分布研究表明，2-硝基咪唑配合物比单硝基咪唑配合物的 4-硝基咪唑类似物具有更好的肿瘤与组织比，但对于 MAMA-双硝基咪唑则不然，因为其脂溶性更高。两种双硝基咪唑化合物的排泄速度更快，肝脏中的背景活性更低，肿瘤与组织的比值更高，比单硝基咪唑更高。更好的生物分布特性使两种 MAMA-双硝基咪唑配合物，特别是（99m）Tc-15，成为潜在的肿瘤缺氧标志物。
