In Vivo Extracellular pH Mapping of Tumors Using Electron Paramagnetic Resonance

Anal Chem. 2018 Dec 4;90(23):13938-13945. doi: 10.1021/acs.analchem.8b03328. Epub 2018 Nov 8.

Abstract

An electron paramagnetic resonance (EPR)-based method for noninvasive three-dimensional extracellular pH mapping was developed using a pH-sensitive nitroxyl radical as an exogenous paramagnetic probe. Fast projection scanning with a constant magnetic field sweep enabled the acquisition of four-dimensional (3D spatial +1D spectral) EPR images within 7.5 min. Three-dimensional maps of pH were reconstructed by processing the pH-dependent spectral information on the images. To demonstrate the proposed method of pH mapping, the progress of extracellular acidosis in tumor-bearing mouse legs was studied. Furthermore, extracellular pH mapping was used to visualize the spatial distribution of acidification in different tumor xenograft mouse models of human-derived pancreatic ductal adenocarcinoma cells. The proposed EPR-based pH mapping method enabled quantitative visualization of regional changes in extracellular pH associated with altered tumor metabolism.

Publication types

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

MeSH terms

  • Animals
  • Carcinoma, Pancreatic Ductal / pathology*
  • Carcinoma, Squamous Cell / pathology*
  • Electron Spin Resonance Spectroscopy
  • Humans
  • Hydrogen-Ion Concentration
  • Imaging, Three-Dimensional*
  • Mice
  • Neoplasms, Experimental / pathology