The cell labeling efficacy, cytotoxicity and relaxivity of copper-activated MRI/PET imaging contrast agents

Biomaterials. 2011 Feb;32(4):1167-76. doi: 10.1016/j.biomaterials.2010.10.013. Epub 2010 Oct 28.

Abstract

A new class of nanoparticle-based dual-modality positron emission tomography/magnetic resonance imaging (PET/MRI) contrast agents has been developed. The probe consists of a superparamagnetic iron oxide (SPIO) or manganese oxide core coated with 3,4-dihydroxy-D,L-phenylalanine (DL-DOPA). The chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was conjugated to DOPA termini. The DOTA modified nanoparticles allow chelation of copper for PET imaging. These surface functionalized nanoparticle-based probes have been characterized by various analytical techniques. The cell-labeling efficacy, cytotoxicity and relaxivity of these nanoparticles have been evaluated and compared with the same properties of one of the most commonly utilized MRI contrast agents, Feridex(®). Evidently, this new nanoparticle has a great potential for use in cell tracking with MRI and PET in the absence of transfecting agent. It is noteworthy that there is a sharp increase in r(2) relaxivity of these nanoparticles on coordination with Cu(2+) ions. Thus these iron oxide nanoparticles can also be explored as the smart magnetic resonance (MR) sensor for the detection of micromolar changes in copper concentration for neurodegenerative diseases such as Alzheimer's disease, Menkes and Wilson's diseases, amyotrophic lateral sclerosis and prion diseases.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chelating Agents / chemistry
  • Contrast Media / chemistry*
  • Contrast Media / metabolism*
  • Copper / chemistry*
  • Dihydroxyphenylalanine / chemistry
  • Dopamine Agents / chemistry
  • Ferrosoferric Oxide / chemistry
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Magnetic Resonance Imaging / instrumentation*
  • Magnetic Resonance Imaging / methods
  • Magnetics
  • Manganese Compounds / chemistry
  • Materials Testing
  • Molecular Structure
  • Nanoparticles / chemistry*
  • Oxides / chemistry
  • Positron-Emission Tomography / instrumentation*
  • Positron-Emission Tomography / methods
  • Rats
  • Rats, Inbred Lew
  • Stem Cells / cytology
  • Stem Cells / physiology

Substances

  • Chelating Agents
  • Contrast Media
  • Dopamine Agents
  • Heterocyclic Compounds, 1-Ring
  • Manganese Compounds
  • Oxides
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • Dihydroxyphenylalanine
  • manganese oxide
  • Copper
  • Ferrosoferric Oxide