title: An estradiol-conjugate for radiolabelling with 177Lu: an attempt to prepare a radiotherapeutic agent.
abstract: 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 6alpha-amino-17beta-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.
authors.affiliation: Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085, India. sharmila@apsara.barc.ernet.in
authors.forename: Sharmila
authors.initials: S
authors.lastname: Banerjee
authors.forename: Tapas
authors.initials: T
authors.lastname: Das
authors.forename: Sudipta
authors.initials: S
authors.lastname: Chakraborty
authors.forename: Grace
authors.initials: G
authors.lastname: Samuel
authors.forename: Aruna
authors.initials: A
authors.lastname: Korde
authors.forename: Meera
authors.initials: M
authors.lastname: Venkatesh
authors.forename: M R A
authors.initials: MR
authors.lastname: Pillai
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D005260:Female; D006573:Heterocyclic Compounds, 1-Ring / Q000627:therapeutic use*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008187:Lutetium / Q000627:therapeutic use*; D010456:Peptides, Cyclic / Q000627:therapeutic use; D011863:Radioimmunoassay; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000627:therapeutic use*
chemical_list: C496695:177Lu-DOTA-lanreotide; D002614:Chelating Agents; D006573:Heterocyclic Compounds, 1-Ring; D007074:Immunoglobulin G; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; D004958:Estradiol; D008187:Lutetium