Rational design, synthesis, and biological evaluation of progesterone-modified MRI contrast agents

Chem Biol. 2007 Jul;14(7):824-34. doi: 10.1016/j.chembiol.2007.06.006.

Abstract

A series of contrast agents for magnetic resonance imaging (MRI) aimed at noninvasively determining the hormone receptor status of cancer in vitro was developed. These MRI contrast agents were prepared by conjugating progesterone to clinically used Gd(III) chelates. These agents exhibited higher progesterone receptor binding affinities in the nanomolar range and intracellular accumulation. High logP values of the modified compounds suggested that the lipophilicity of the steroid conjugates may have contributed to membrane permeability. Synchrotron radiation X-ray fluorescence microscopy and magnetic resonance images revealed that the synthesized conjugates showed the greatest cellular accumulation and significant increase in relaxivity in vitro compared to the previously developed steroid-modified agent. Transcriptional assays using the progesterone response element linked to luciferase indicated that the contrast agents entered the cell, interacted with the biological target, and drove specific progesterone-mediated transcription.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Breast Neoplasms / pathology
  • Contrast Media*
  • Drug Design*
  • Drug Evaluation, Preclinical*
  • Gadolinium / metabolism
  • Humans
  • Magnetic Resonance Imaging*
  • Microscopy, Fluorescence
  • Progesterone / chemistry*
  • Receptors, Progesterone / metabolism

Substances

  • Contrast Media
  • Receptors, Progesterone
  • Progesterone
  • Gadolinium