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

Abstract

To assist in the development of technetium-based radiopharmaceuticals that are useful for the diagnostic imaging of steroid receptor-positive breast tumors, 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 radioactive technetium. The metal chelates contain the rhenium metal in several oxidation states, being +5, +3, and +1, and they were attached to 21-substituted progesterone derivatives. A competitive receptor-binding assay (rat uterine cytosol, 0°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, containing a NMe group as the central donor atom in the tridentate ligand part. This value reflects a relative binding affinity of 75% compared with the parent steroid progesterone.