Bivalent Approach for Homodimeric Estradiol Based Ligand: Synthesis and Evaluation for Targeted Theranosis of ER(+) Breast Carcinomas

The synthesis of estradiol based bivalent ligand [(EST)2DT] is reported and its potential for targeted imaging and therapy of ER(+) tumors has been evaluated. For the purpose, ethinylestradiol was functionalized with an azidoethylamine moiety via click chemistry. The resultant derivative was reacted in a bivalent mode with DTPA-dianhydride to form the multicoordinate chelating agent, (EST)2DT which displayed capability to bind 99mTc. The radiolabeled complex, 99mTc-(EST)2DT was obtained in >99% radiochemical purity and 20–48 GBq/μmol of specific activity. RBA assay revealed ∼15% binding with estrogen receptor. Evaluation of ligand on ER(+)-cell line (MCF-7) suggested enhanced and ER-mediated uptake. In vivo assays displayed early tracer accumulation in MCF-7 xenografts with tumor to muscle ratio ∼6 in 2 h and negligible uptakes in nontargeted organs. MTT assay performed on ER(+) and ER(−) cell lines displayed selective inhibition of ER(+) cancer cell growth with IC50 = 14.3 μM which was comparable to tamo...