Evaluation of Re and (99m)Tc complexes of 2-(4'-aminophenyl)benzothiazole as potential breast cancer radiopharmaceuticals.
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.
Institute of Biology, National Centre for Scientific Research Demokritos, 15310 Athens, Greece.
Stamatia
S
Tzanopoulou
Marina
M
Sagnou
Maria
M
Paravatou-Petsotas
Eleni
E
Gourni
George
G
Loudos
Stavros
S
Xanthopoulos
Daniel
D
Lafkas
Hippokratis
H
Kiaris
Alexandra
A
Varvarigou
Ioannis C
IC
Pirmettis
Minas
M
Papadopoulos
Maria
M
Pelecanou
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000532:radiotherapy; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D012211:Rhenium; D013329:Structure-Activity Relationship; D013667:Technetium; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D052160:Benzothiazoles; D056831:Coordination Complexes; D019275:Radiopharmaceuticals; D012211:Rhenium; D013667:Technetium