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Preparation, Purification, and Characterization of Lanthanide Complexes for Use as Contrast Agents for Magnetic Resonance Imaging
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Published on: July 21, 2011

Copper-responsive magnetic resonance imaging contrast agents.

Emily L Que1, Eliana Gianolio, Suzanne L Baker

  • 1Department of Chemistry, University of California, Berkeley, California 94720, USA.

Journal of the American Chemical Society
|June 4, 2009
PubMed
Summary
This summary is machine-generated.

New Copper-Gad (CG) contrast agents enhance MRI relaxivity upon copper binding. These agents show high selectivity and enable visualization of copper level changes via MRI.

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Area of Science:

  • Chemical Biology
  • Medical Imaging
  • Nanotechnology

Background:

  • Magnetic Resonance Imaging (MRI) contrast agents are crucial for medical diagnostics.
  • Developing responsive contrast agents that signal specific analytes is an active area of research.
  • Copper ions play vital roles in biological processes, and their dysregulation is linked to diseases.

Purpose of the Study:

  • To design, synthesize, and evaluate a novel family of copper-activated MRI contrast agents, termed Copper-Gad (CG).
  • To investigate the mechanism of copper-induced relaxivity switching in these agents.
  • To assess the potential of CG sensors for visualizing copper level changes using MRI.

Main Methods:

  • Synthesis of the Copper-Gad (CG) family, featuring a Gd(3+)-DO3A core linked to thioether-rich receptors.
  • Evaluation of longitudinal relaxivity (r(1)) in the presence and absence of copper ions (Cu+ and Cu2+).
  • Assessment of selectivity against competing metal ions and mechanism elucidation using (17)O NMR and nuclear magnetic relaxation dispersion (NMRD).
  • T(1)-weighted phantom MRI to demonstrate visualization of copper level changes.

Main Results:

  • CG agents exhibit low baseline relaxivity, which significantly increases upon binding Cu+ or Cu2+.
  • CG2 and CG3 demonstrated a 360% increase in relaxivity upon Cu+ binding.
  • The sensors show high selectivity for copper ions over other biologically relevant metal ions like Zn2+.
  • Mechanism studies indicate copper binding alters the Gd(3+) coordination environment, increasing relaxivity.

Conclusions:

  • The Copper-Gad (CG) family represents a new class of effective copper-activated MRI contrast agents.
  • These agents offer a promising tool for non-invasive MRI-based detection and quantification of copper levels.
  • The developed sensors have potential applications in diagnosing and monitoring diseases associated with copper dysregulation.