An estradiol-conjugate for radiolabelling with 177Lu: an attempt to prepare a radiotherapeutic agent

177Lu is presently being considered as one of the most promising radionuclide for targeted therapy owing to its suitable decay characteristics. 177Lu in high radionuclidic purity (99.99%) and moderate specific activity (100–110 TBq/g) was produced using enriched (60.6% 176Lu) Lu2O3 target. The macrocycle 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is known to form stable complexes with lanthanides. Herein, we describe a novel attempt to introduce 177Lu in the estradiol moiety through a steroidal–BFCA (Bifunctional Chelating Agent) conjugate. The preparation of a steroid conjugate via coupling of 6α-amino-17β-estradiol with a C-functionalized DOTA derivative viz. p-NCS-benzyl-DOTA as a BFCA and thereafter the radiolabelling of the conjugate with 177Lu is reported. Biological activity of the resultant estradiol–DOTA conjugate after radiolabelling was studied by carrying out preliminary in vitro cell uptake studies with MCF-7, human breast carcinoma cell line expressing estrogen receptors as well as binding studies with anti-estradiol antibodies.

A novel approach towards the preparation of a radiolabelled steroidal–BFCA conjugate via coupling of 6α-amino-17β-estradiol with a C-functionalized DOTA derivative viz. p-thiocyanato-benzyl-DOTA is reported. The conjugate has been radiolabelled with 177Lu, a promising therapeutic radionuclide and its preliminary biological behaviour has been studied.Figure optionsDownload as PowerPoint slide