Toward development of targeted nonsteroidal antiandrogen-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-gadolinium complex for prostate cancer diagnostics

J Med Chem. 2010 Sep 9;53(17):6316-25. doi: 10.1021/jm100289b.

Abstract

Androgen receptors are present in most advanced prostate cancer specimens, having a critical role in development of this type of cancer. For correct prognosis of patient conditions and treatment monitoring, noninvasive imaging techniques have great advantages over surgical procedures. We developed synthetic methodologies for preparation of novel androgen receptor-targeting agents in an attempt to build a versatile platform for prostate cancer imaging and treatment. The structure of these compounds comprises of a lanthanoid metal ion, gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (Gd-DOTA)-based binding fragment and, connected to it by a flexible linker, bicalutamide-derived nonsteroidal antiandrogen moiety. A representative gadolinium complex 15 was evaluated as a magnetic resonance imaging (MRI) agent in C57/bl6 male mouse bearing orthotopic TRAMP C2 prostate tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / chemical synthesis*
  • Androgen Antagonists / chemistry
  • Androgen Antagonists / metabolism
  • Anilides / chemical synthesis*
  • Anilides / chemistry
  • Anilides / metabolism
  • Animals
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / chemistry
  • Coordination Complexes / metabolism
  • Gadolinium*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / metabolism
  • Receptors, Androgen / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Androgen Antagonists
  • Anilides
  • Coordination Complexes
  • Receptors, Androgen
  • Gadolinium