Divalent metal transporter, DMT1: A novel MRI reporter protein

Authors

  • Benjamin B. Bartelle,

    1. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York, USA
    2. Molecular Biophysics Graduate Program, New York University School of Medicine, New York, New York, USA
    Search for more papers by this author
  • Kamila U. Szulc,

    1. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York, USA
    2. Biomedical Imaging Graduate Program, New York University School of Medicine, New York, New York, USA
    Search for more papers by this author
  • Giselle A. Suero-Abreu,

    1. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York, USA
    2. Biomedical Imaging Graduate Program, New York University School of Medicine, New York, New York, USA
    Search for more papers by this author
  • Joe J. Rodriguez,

    1. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York, USA
    Search for more papers by this author
  • Daniel H. Turnbull

    Corresponding author
    1. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York, USA
    2. Molecular Biophysics Graduate Program, New York University School of Medicine, New York, New York, USA
    3. Biomedical Imaging Graduate Program, New York University School of Medicine, New York, New York, USA
    4. Department of Radiology, New York University School of Medicine, New York, New York, USA
    5. Department of Pathology, New York University School of Medicine, New York, New York, USA
    • Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016. E-mail: daniel.turnbull@med.nyu.edu

    Search for more papers by this author

Abstract

Manganese (Mn)-enhanced MRI (MEMRI) has found a growing number of applications in anatomical and functional imaging in small animals, based on the cellular uptake of Mn ions in the brain, heart, and other organs. Previous studies have relied on endogenous mechanisms of paramagnetic Mn ion uptake and enhancement. To genetically control MEMRI signals, we reverse engineered a major component of the molecular machinery involved in Mn uptake, the divalent metal transporter, DMT1. DMT1 provides positive cellular enhancement in a manner that is highly sensitive and dynamic, allowing greater spatial and temporal resolution for MRI compared to previously proposed MRI reporters such as ferritin. We characterized the MEMRI signal enhancement properties of DMT1-expressing cells, both in vitro and in vivo in mouse models of cancer and brain development. Our results show that DMT1 provides an effective genetic MRI reporter for a wide range of biological and preclinical imaging applications. Magn Reson Med 70:842–850, 2013. © 2012 Wiley Periodicals, Inc.

Ancillary