Imaging in vivo extracellular pH with a single paramagnetic chemical exchange saturation transfer magnetic resonance imaging contrast agent

Guanshu Liu, Yuguo Li, Vipul R. Sheth, Mark D. Pagel

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

The measurement of extracellular pH (pH e) has potential utility for cancer diagnoses and for assessing the therapeutic effects of pHdependent therapies. A single magnetic resonance imaging (MRI) contrast agent that is detected through paramagnetic chemical exchange saturation transfer (PARACEST) was designed to measure tumor pH e throughout the range of physiologic pH and with magnetic resonance saturation powers that are not harmful to a mouse model of cancer. The chemical characterization and modeling of the contrast agent Yb 3+-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid,10-o-aminoanilide (Yb-DO3A-oAA) suggested that the aryl amine of the agent forms an intramolecular hydrogen bond with a proximal carboxylate ligand, which was essential for generating a practical chemical exchange saturation transfer (CEST) effect from an amine. A ratio of CEST effects from the aryl amine and amide was linearly correlated with pH throughout the physiologic pH range. The pH calibration was used to produce a parametric pH map of a subcutaneous flank tumor on a mouse model of MCF-7 mammary carcinoma. Although refinements in the in vivo CEST MRI methodology may improve the accuracy of pH e measurements, this study demonstrated that the PARACEST contrast agent can be used to generate parametric pH maps of in vivo tumors with saturation power levels that are not harmful to a mouse model of cancer.

Original languageEnglish (US)
Pages (from-to)47-57
Number of pages11
JournalMolecular imaging
Volume11
Issue number1
DOIs
StatePublished - Jan 1 2012

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Biomedical Engineering
  • Radiology Nuclear Medicine and imaging
  • Condensed Matter Physics

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