Synthesis of a novel antiestrogen radioligand (99mTc-TOR-DTPA)

This study was aimed at developing a hydrophilic radioligand as an antiestrogen drug derivative to be used for imaging breast tumors. Toremifene [TOR; 4-chloro-1,2-diphenyl-1-(4-(2-(N,N-di-methylamino)ethoxy)phenyl)-1-butene, as citrate salt] was selected as the starting material to be derived, since it has been used extensively as an antiestrogen drug for treatment and prevention of human breast cancer. An antiestrogen drug derivative, TOR attached to diethylenetriamine pentaacetic acid (DTPA), was synthesized by two experimental treatments, including a purification and a reaction step. We described the synthesis of this TOR derivative, (3Z)-4-{4-[2-(dimethylamino) ethoxy] phenyl}-3,4-diphenylbut-3-en-1-ylN,N-bis[2-(2,6-dioxomorpholin-4-yl)ethyl]glycinate (TOR-DTPA), in detail. Mass spectroscopy confirmed the expected structures. TOR-DTPA was labeled with technetium-99m ((99m)Tc), using stannous chloride (SnCl(2)) as the reducing agent. Biodistribution studies were performed on female Albino Wistar rats. Quality controls, radiochemical yield, and stability studies were done utilizing high-performance liquid chromatography, radioelectrophoresis, thin-layer chromatography, and thin-layer radiochromatography methods. The synthesized compound was found to be hydrophilic and anionic, with high stability for the duration of the testing period in vitro. The results indicated that the radiolabeled compound has estrogen-receptor specificity, especially for the breast tissue. It is highly possible that this compound could be used for imaging breast tumors as a novel technetium-labeled hydrophilic estrogen derivative radioligand.