Radioiodinated ligands for the estrogen receptor: effect of different 7-cyanoalkyl chains on the binding affinity of novel iodovinyl-6-dehydroestradiols

Appl Radiat Isot. 2009 Feb;67(2):301-7. doi: 10.1016/j.apradiso.2008.10.005. Epub 2008 Oct 21.

Abstract

Three novel 17 alpha-ethynyl-Delta(6,7)-estra-3,17beta-diols and their 17 alpha-[(125)I]-iodovinyl derivatives, containing different C7-cyanoalkyl chains, were studied as potential radioligands for the estrogen receptor. The influence of the chain length on the biological behaviour of the compounds was assessed through in vitro ER binding assays of the ethynyl derivatives and breast cancer cell uptake studies of the 17 alpha-[(125)I]-iodovinyl-Delta(6,7)-estra-3,17beta-diols. A difference in alkyl chain induced a decrease in ER binding affinities of substances, however, the receptor-binding affinities (RBA) of all compounds were lower than that of estradiol itself. In addition, a non-specific cell binding was observed which is in accordance with the encountered ethynyl RBA values suggesting that the uptake is not ER mediated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkanes
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Estradiol / analogs & derivatives*
  • Estradiol / chemistry
  • Estradiol / pharmacokinetics*
  • Female
  • Humans
  • Iodine Radioisotopes / pharmacokinetics*
  • Ligands
  • Nitriles
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics
  • Receptors, Estrogen / analysis
  • Receptors, Estrogen / metabolism*
  • Structure-Activity Relationship

Substances

  • Alkanes
  • Iodine Radioisotopes
  • Ligands
  • Nitriles
  • Radiopharmaceuticals
  • Receptors, Estrogen
  • Estradiol