Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide

Biochem Biophys Res Commun. 2014 Dec 12;455(3-4):246-50. doi: 10.1016/j.bbrc.2014.10.155. Epub 2014 Nov 6.

Abstract

Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images.

Keywords: Contrast agents; Cyclic RGD peptide; Gd-DOTA; MRI; Tumor targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Contrast Media / chemistry*
  • Cycloparaffins / chemistry*
  • Female
  • Gadolinium / chemistry
  • Heterocyclic Compounds / chemistry*
  • Humans
  • Integrins / chemistry
  • Kidney / metabolism
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Oligopeptides / chemistry*
  • Organometallic Compounds / chemistry*
  • Protein Binding
  • Urinary Bladder / metabolism

Substances

  • Contrast Media
  • Cycloparaffins
  • Heterocyclic Compounds
  • Integrins
  • Oligopeptides
  • Organometallic Compounds
  • arginyl-glycyl-aspartic acid
  • gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
  • Gadolinium