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 "Marty" Pagel

Research output: Contribution to journalArticle

68 Citations (Scopus)

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 2012

Fingerprint

Magnetic resonance
Contrast Media
magnetic resonance
Magnetic Resonance Imaging
saturation
Imaging techniques
Tumors
Amines
cancer
mice
Neoplasms
amines
tumors
Amides
Hydrogen bonds
Ligands
Calibration
Therapeutic Uses
Acids
carboxylates

ASJC Scopus subject areas

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

Cite this

Imaging in vivo extracellular pH with a single paramagnetic chemical exchange saturation transfer magnetic resonance imaging contrast agent. / Liu, Guanshu; Li, Yuguo; Sheth, Vipul R.; Pagel, Mark "Marty".

In: Molecular Imaging, Vol. 11, No. 1, 01.2012, p. 47-57.

Research output: Contribution to journalArticle

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