Technetium- and rhenium-labeled progestins: synthesis, receptor binding and in vivo distribution of an 11 beta-substituted progestin labeled with technetium-99 and rhenium-186

J Nucl Med. 1992 Apr;33(4):558-69.

Abstract

In an effort to develop radiopharmaceuticals useful for the diagnostic imaging of steroid receptor-positive breast tumors, we have radiolabeled an analog of the antiprogestin RU486 (mifepristone), modified to incorporate an N2S2 chelate system in the 11 beta-position, with 99Tc, 99mTc, and 186Re. For the 99Tc-labeled analogs (3), a syn pair and two individual antidiastereomers (linker methylene versus metal-oxo, relative to the N2S2 plane) were isolated. In competitive radiometric binding assays, the syn pair (3syn1,2) had affinity for the progesterone receptor that was 25% that of (promegestone) R5020 (or 161% that of progesterone), and the individual anti-diastereomers had affinities of 47% (3anti1) and 7% (3anti2) that of R5020 (or 303% and 45% that of progesterone). The specific-to-nonspecific binding ratio of the 99mTc (4) and 186Re (5) 11 beta-linked syn systems are 75/25 and 54/46, respectively. In vivo, conjugates 4 and 5 showed progesterone receptor-mediated uptake in rat uterus, but also high uptake in non-target tissues, presumably because of the high lipophilicity of the metal complexes. Modified systems may be useful in vivo as receptor-directed agents for diagnostic imaging or treatment of steroid receptor-positive tumors.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Female
  • Isotope Labeling
  • Mifepristone / analogs & derivatives*
  • Mifepristone / chemical synthesis
  • Mifepristone / pharmacokinetics
  • Organotechnetium Compounds / chemical synthesis
  • Organotechnetium Compounds / pharmacokinetics*
  • Radioisotopes / pharmacokinetics*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Progesterone / metabolism*
  • Rhenium / pharmacokinetics*
  • Technetium
  • Tissue Distribution
  • Uterus / metabolism

Substances

  • Organotechnetium Compounds
  • Radioisotopes
  • Receptors, Progesterone
  • Mifepristone
  • Rhenium
  • Technetium