Synthesis of novel progestin-rhenium conjugates as potential ligands for the progesterone receptor

To assist in the development of technetium-based radiopharmaceuticals that are useful for the diagnostic imaging of steroid receptor-positive breast t umors, we have synthesized a series of small-sized metal chelates according to 'n + 1' mixed-ligand, thioether-carbonyl and organometallic designs. In these preliminary investigations, rhenium was used as a model for the radi oactive technetium. The metal chelates contain the rhenium metal in several oxidation states, being +5, +3, and +1, and they were attached to 21-subst ituted progesterone derivatives. A competitive receptor-binding assay (rat uterine cytosol, 0 degrees C) was used to determine the binding affinity of these conjugates for the progesterone receptor. The highest affinity of 9% (RU5020 = 100%) was obtained with a '3 + 1' mixed-ligand complex, containi ng a NMe group as the central donor atom in the tridentate ligand part. Thi s value reflects a relative binding affinity of 75% compared with the paren t steroid progesterone. (C) 1999 Elsevier Science Ltd. All rights reserved.