Institute of Biology, National Centre for Scientific Research Demokritos, 15310 Athens, Greece.
J Med Chem. 2010 Jun 24;53(12):4633-41. doi: 10.1021/jm1001293.
The synthesis of M(I)(CO)(3)(NNO) (M = Re, (99m)Tc) complexes conjugated to the antitumor agent 2-(4'-aminophenyl)benzothiazole and to its 6-methyl derivative, as well as their in vitro and in vivo biological evaluation as breast cancer radiopharmaceuticals, is reported. The Re complexes displayed under the fluorescence microscope clear uptake by the sensitive to the 2-(4'-aminophenyl)benzothiazole pharmacophore breast cancer cell lines MCF-7 and T47D, while uptake by less sensitive lines and by normal fibroblasts was much weaker. In accordance, uptake of the corresponding radioactive (99m)Tc complexes was clearly higher in the breast cancer cell lines MCF-7 and MDA-231 compared to normal fibroblasts. Biodistribution of the (99m)Tc complexes in SCID mice bearing MCF-7 xenografts showed appreciable tumor uptake. A tumor/muscle ratio of 2.2 was measured for the complex conjugated to 2-(4'-aminophenyl)benzothiazole that led to successful tumor imaging. The results render the 2-(4'-aminophenyl)benzothiazole complexes potential candidates for imaging ((99m)Tc) and targeted radiotherapy ((188)Re) of breast cancer.
报告了将抗肿瘤剂 2-(4'-氨基苯基)苯并噻唑及其 6-甲基衍生物与 M(I)(CO)(3)(NNO)（M = Re，(99m)Tc）配合物缀合的合成，以及它们作为乳腺癌放射性药物的体外和体内生物学评价。在荧光显微镜下，Re 配合物对敏感于 2-(4'-氨基苯基)苯并噻唑药效团的乳腺癌细胞系 MCF-7 和 T47D 有明显的摄取，而对不太敏感的细胞系和正常成纤维细胞的摄取则弱得多。相应地，放射性 (99m)Tc 配合物在乳腺癌细胞系 MCF-7 和 MDA-231 中的摄取明显高于正常成纤维细胞。在携带 MCF-7 异种移植瘤的 SCID 小鼠中的生物分布研究表明，(99m)Tc 配合物具有可观的肿瘤摄取。对于与 2-(4'-氨基苯基)苯并噻唑缀合的复合物，测得肿瘤/肌肉比为 2.2，这使其能够成功进行肿瘤成像。这些结果表明，2-(4'-氨基苯基)苯并噻唑配合物是乳腺癌成像 ((99m)Tc) 和靶向放射治疗 ((188)Re) 的潜在候选物。
