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: Sharmila Banerjee, Tapas Das, Sudipta Chakraborty, Grace Samuel, Aruna Korde, Meera Venkatesh, M R A Pillai
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 13 Issue 13 Pg. 4315-22 (Jul 01 2005) ISSN: 0968-0896 [Print] England
• PMID: 15927837 (Publication Type: Journal Article)

Chemical References

• 177Lu-DOTA-lanreotide
• Chelating Agents
• Heterocyclic Compounds, 1-Ring
• Immunoglobulin G
• Peptides, Cyclic
• Radiopharmaceuticals
• Estradiol
• Lutetium

Topics

• Breast Neoplasms (metabolism, radiotherapy)
• Cell Line, Tumor
• Chelating Agents (metabolism)
• Estradiol (analogs & derivatives, chemical synthesis, therapeutic use)
• Female
• Heterocyclic Compounds, 1-Ring (therapeutic use)
• Humans
• Immunoglobulin G (metabolism)
• Lutetium (therapeutic use)
• Peptides, Cyclic (therapeutic use)
• Radioimmunoassay
• Radiopharmaceuticals (chemical synthesis, therapeutic use)