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

Lu-177 is presently being considered as one of the most promising radionuclide for targeted therapy owing to its suitable decay characteristics. Lu-177 in high radionuclidic purity (99.99%) and moderate specific activity (100-110 TBq/g) was produced using enriched (60.6% Lu-176) 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 Lu-177 in the estradiol moiety through a steroidal-BFCA (Bifunctional Chelating Agent) conjugate. The preparation of a steroid conjugate via coupling of 6 alpha-amino-17 beta-estradiol with a C-functionalized DOTA derivative viz. p-NCS-benzyl-DOTA as a BFCA and thereafter the radio-labelling of the conjugate with Lu-177 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. (c) 2005 Elsevier Ltd. All rights reserved.