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

被引：90

作者：

Tzanopoulou, Stamatia ^{[1
]}

Sagnou, Marina ^{[1
]}

Paravatou-Petsotas, Maria ^{[2
]}

Gourni, Eleni ^{[2
]}

Loudos, George ^{[3
]}

Xanthopoulos, Stavros ^{[2
]}

Lafkas, Daniel ^{[4
]}

Kiaris, Hippokratis ^{[4
]}

Varvarigou, Alexandra ^{[2
]}

Pirmettis, Ioannis C. ^{[2
]}

Papadopoulos, Minas ^{[2
]}

Pelecanou, Maria ^{[1
]}

机构：

[1] Natl Ctr Sci Res Demokritos, Inst Biol, Athens 15310, Greece

[2] Natl Ctr Sci Res Demokritos, Inst Radioisotopes Radiodiagnost Prod, Athens 15310, Greece

[3] Inst Educ Technol, Dept Med Instruments Technol, Athens 12210, Greece

[4] Univ Athens, Sch Med, Dept Biol Chem, GR-11527 Athens, Greece

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 53卷 / 12期

关键词：

ANTITUMOR BENZOTHIAZOLES; IN-VITRO; BIOLOGICAL EVALUATION; TECHNETIUM; 2-(4-AMINOPHENYL)BENZOTHIAZOLES; CHEMISTRY; RHENIUM; CELLS; 2-(4-AMINO-3-METHYLPHENYL)BENZOTHIAZOLE; GROWTH;

D O I：

10.1021/jm1001293

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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

引用

页码：4633 / 4641

页数：9

共 34 条

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