title: Noninvasive detection of enzyme activity in tumor models of human ovarian cancer using catalyCEST MRI.
abstract: We proposed to detect the in vivo enzyme activity of γ-glutamyl transferase (GGT) within mouse models of human ovarian cancers using catalyCEST MRI with a diamagnetic CEST agent.
  
  
  
  A CEST-FISP MRI protocol and a diamagnetic CEST agent were developed to detect GGT enzyme activity in biochemical solution. A quantitative Michaelis-Menten enzyme kinetics study was performed to confirm that catalyCEST MRI can measure enzyme activity. In vivo catalyCEST MRI studies generated pixel-wise activity maps of GGT activities. Ex vivo fluorescence imaging was performed for validation.
  
  
  
  CatalyCEST MRI selectively detected two CEST signals from a single CEST agent, whereby one CEST signal was responsive to GGT enzyme activity and the other CEST signal was an unresponsive control signal. The comparison of these CEST signals facilitated in vivo catalyCEST MRI studies that detected high GGT activity in OVCAR-8 tumors, low GGT activity in OVCAR-3 tumors, and low or no GGT activity in muscle tissues.
  
  
  
  CatalyCEST MRI with a diamagnetic CEST agent can detect the level of GGT enzyme activity within in vivo tumor models of human ovarian cancers. Magn Reson Med 77:2005-2014, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona, USA.
authors.forename: Sanhita
authors.initials: S
authors.lastname: Sinharay
authors.affiliation: Department of Medical Imaging, University of Arizona, Tucson, Arizona, USA.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Randtke
authors.affiliation: Biomedical Engineering Graduate Interdisciplinary Program, University of Arizona, Tucson, Arizona, USA.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Jones
authors.affiliation: Department of Medical Imaging, University of Arizona, Tucson, Arizona, USA.
authors.forename: Christine M
authors.identifier: 0000-0001-7878-961X
authors.initials: CM
authors.lastname: Howison
authors.affiliation: Department of Obstetrics and Gynecology, University of Arizona, Tucson, Arizona, USA.|University of Arizona Cancer Center, University of Arizona, Tucson, Arizona, USA.
authors.forename: Setsuko K
authors.initials: SK
authors.lastname: Chambers
authors.affiliation: Laboratory of Molecular Theranostics, National Cancer Institute, NIH, Bethesda, Maryland, USA.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona, USA.|Department of Medical Imaging, University of Arizona, Tucson, Arizona, USA.|University of Arizona Cancer Center, University of Arizona, Tucson, Arizona, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Pagel
mesh_terms: D000818:Animals; D002384:Catalysis; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry; D004195:Disease Models, Animal; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D005998:Glycine / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D010455:Peptides / Q000737:chemistry; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D003287:Contrast Media; D005456:Fluorescent Dyes; D010455:Peptides; D005723:gamma-Glutamyltransferase; D003545:Cysteine; D005998:Glycine
keywords: CEST MRI; enzyme activity; glutamyl transferase; molecular imaging; ovarian cancer