Synthesis and binding affinities of new 17 alpha-substituted estradiol-rhenium "n+1" mixed-ligand and thioethercarbonyl complexes

The development of technetium and rhenium-based radiotracers for the steroi d receptor system requires the use of suitable donor groups on the steroid to provide stable binding sites for the metal. Previous approaches have mai nly exploited methods involving various N- and S-coordinating chelate syste ms or organometallic complexes. In this work we have prepared several novel chelate systems attached to a series of 17 alpha-substituted estradiol der ivatives and examined their binding to the estrogen receptor (ER). The neut ral "n+1" mixed-ligand and dithioether-carbonyl complexes that we prepared contain the metal in three oxidation states, +5, +3 or fl, attached to a 17 alpha-substituted estradiol derivative through a thiol group, an isocyanid e group, or a dithioether unit, respectively. In our preliminary investigat ions, Mle used rhenium as a nonradioactive analog of the radionuclide techn etium. All complexes synthesized were evaluated in a competitive radiometri c receptor binding assay at 0 degrees C and 25 degrees C to determine their relative binding affinities (RBA) to the ER (relative to 3,17 beta-estradi ol, RBA = 100%). The complexes show binding affinities Icp to 23.4% at 0 de grees C and 14.1% at 25 degrees C. (Steroids 63:665-671, 1998) (C) 1998 by Elsevier Science Inc.