Evaluation of Re and 99mTc Complexes of 2-(4′-Aminophenyl)benzothiazole as Potential Breast Cancer Radiopharmaceuticals

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• 作者：Stamatia Tzanopoulou ; Marina Sagnou ; Maria Paravatou-Petsotas ; Eleni Gourni ; George Loudos ; Stavros Xanthopoulos ; Daniel Lafkas ; Hippokratis Kiaris ; Alexandra Varvarigou ; Ioannis C. Pirmettis ; Minas P
• 刊名：Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：June 24, 2010
• 年：2010
• 卷：53
• 期：12
• 页码：4633-4641
• 全文大小：890K
• 年卷期：v.53,no.12(June 24, 2010)
• ISSN：1520-4804

文摘

The synthesis of M(I)(CO)₃(NNO) (M = Re, ^99mTc) 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 ^99mTc complexes was clearly higher in the breast cancer cell lines MCF-7 and MDA-231 compared to normal fibroblasts. Biodistribution of the ^99mTc 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 (^99mTc) and targeted radiotherapy (¹⁸⁸Re) of breast cancer.