Non-invasive imaging using reporter genes altering cellular water permeability

Nat Commun. 2016 Dec 23:7:13891. doi: 10.1038/ncomms13891.

Abstract

Non-invasive imaging of gene expression in live, optically opaque animals is important for multiple applications, including monitoring of genetic circuits and tracking of cell-based therapeutics. Magnetic resonance imaging (MRI) could enable such monitoring with high spatiotemporal resolution. However, existing MRI reporter genes based on metalloproteins or chemical exchange probes are limited by their reliance on metals or relatively low sensitivity. Here we introduce a new class of MRI reporters based on the human water channel aquaporin 1. We show that aquaporin overexpression produces contrast in diffusion-weighted MRI by increasing tissue water diffusivity without affecting viability. Low aquaporin levels or mixed populations comprising as few as 10% aquaporin-expressing cells are sufficient to produce MRI contrast. We characterize this new contrast mechanism through experiments and simulations, and demonstrate its utility in vivo by imaging gene expression in tumours. Our results establish an alternative class of sensitive, metal-free reporter genes for non-invasive imaging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aquaporins / genetics
  • Aquaporins / metabolism
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • CHO Cells
  • Cell Line, Tumor
  • Cricetulus
  • Diffusion Magnetic Resonance Imaging / methods*
  • Gene Expression
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism*
  • HEK293 Cells
  • Humans
  • Mice, SCID
  • Permeability
  • Transplantation, Heterologous
  • Water / metabolism*

Substances

  • Aquaporins
  • Water
  • Green Fluorescent Proteins