title: Rational design, synthesis, and biological evaluation of progesterone-modified MRI contrast agents.
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.
authors.affiliation: Departments of Chemistry, Biochemistry and Molecular, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Jiyoun
authors.initials: J
authors.lastname: Lee
authors.forename: Joanna E
authors.initials: JE
authors.lastname: Burdette
authors.forename: Keith W
authors.initials: KW
authors.lastname: MacRenaris
authors.forename: Devkumar
authors.initials: D
authors.lastname: Mustafi
authors.forename: Teresa K
authors.initials: TK
authors.lastname: Woodruff
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Meade
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology; D003287:Contrast Media; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005682:Gadolinium / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008856:Microscopy, Fluorescence; D011374:Progesterone / Q000737:chemistry*; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D003287:Contrast Media; D011980:Receptors, Progesterone; D011374:Progesterone; D005682:Gadolinium