title: Evaluations of extracellular pH within in vivo tumors using acidoCEST MRI.
abstract: OBJECTIVE
  A practical, noninvasive method is needed to measure the extracellular pH (pHe) within in vivo tumors to longitudinally monitor tumor acidosis. We have optimized a biomedical imaging method, termed acidoCEST MRI, to provide noninvasive assessments of tumor pHe in preclinical models of mammary carcinoma.
  
  
  METHODS
  A CEST-FISP MRI method was optimized to detect the chemical exchange saturation transfer (CEST) of two amide protons of a clinically approved CT contrast agent, iopromide. The ratio of the two CEST effects was used to measure pH. Routes of administration of iopromide were evaluated to ensure sufficient delivery of the agent to the tumor. The optimized acidoCEST MRI method was then used to evaluate the change in tumor pHe following alkalinizing bicarbonate treatment.
  
  
  RESULTS
  The acidoCEST MRI protocol measured pH between 6.2 and 7.2 pH units. Greater delivery of iopromide was shown to improve the precision of the measurement of tumor pHe, but the agent did not influence the tumor pHe. AcidoCEST MRI was used to longitudinally monitor the effect of bicarbonate treatment on the pHe of tumors and bladders.
  
  
  CONCLUSIONS
  This study demonstrates that an optimized acidoCEST MRI method is a practical, noninvasive method for assessing changes in tumor acidosis.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona, USA.
authors.forename: Liu Qi
authors.initials: LQ
authors.lastname: Chen
authors.forename: Christine M
authors.initials: CM
authors.lastname: Howison
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Jeffery
authors.forename: Ian F
authors.initials: IF
authors.lastname: Robey
authors.forename: Phillip H
authors.initials: PH
authors.lastname: Kuo
authors.forename: Mark D
authors.initials: MD
authors.lastname: Pagel
mesh_terms: D000138:Acidosis / Q000175:diagnosis; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D003287:Contrast Media / Q000008:administration & dosage / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007472:Iohexol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008325:Mammary Neoplasms, Experimental / Q000737:chemistry*; D051379:Mice; D055114:X-Ray Microtomography
chemical_list: D001639:Bicarbonates; D003287:Contrast Media; D007472:Iohexol; C038192:iopromide
keywords: CEST MRI; CEST-FISP; bicarbonate treatment; iopromide; tumor pH