In vitro molecular magnetic resonance imaging detection and measurement of apoptosis using superparamagnetic iron oxide + antibody as ligands for nucleosomes

Phys Med Biol. 2012 Nov 7;57(21):7015-28. doi: 10.1088/0031-9155/57/21/7015. Epub 2012 Oct 10.

Abstract

Recent research in cell biology as well as oncology research has focused on apoptosis or programmed cell death as a means of quantifying the induced effects of treatment. A hallmark of late-stage apoptosis is nuclear fragmentation in which DNA is degraded to release nucleosomes with their associated histones. In this work, a method was developed for detecting and measuring nucleosome concentration in vitro with magnetic resonance imaging (MRI). The indirect procedure used a commercially available secondary antibody-superparamagnetic iron oxide (SPIO) particle complex as a contrast agent that bound to primary antibodies against nucleosomal histones H4, H2A and H2B. Using a multiple-echo spin-echo sequence on a 1.5 T clinical MRI scanner, significant T₂ relaxation enhancement as a function of in vitro nucleosomal concentration was measured. In addition, clustering or aggregation of the contrast agent was demonstrated with its associated enhancement in T₂ effects. The T₂ clustering enhancement showed a complex dependence on relative concentrations of nucleosomes, primary antibody and secondary antibody + SPIO. The technique supports the feasibility of using MRI measurements of nucleosome concentration in blood as a diagnostic, prognostic and predictive tool in the management of cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / immunology*
  • Apoptosis*
  • Blood Circulation
  • Feasibility Studies
  • Ferric Compounds / chemistry*
  • Ferric Compounds / metabolism*
  • HL-60 Cells
  • Humans
  • Ligands
  • Magnetic Resonance Imaging / methods*
  • Magnets / chemistry*
  • Microspheres
  • Nucleosomes / metabolism*
  • Prognosis
  • Reproducibility of Results

Substances

  • Antibodies
  • Ferric Compounds
  • Ligands
  • Nucleosomes
  • ferric oxide