title: Detection of in vivo enzyme activity with CatalyCEST MRI.
abstract: OBJECTIVE
  CatalyCEST MRI compares the detection of an enzyme-responsive chemical exchange saturation transfer (CEST) agent with the detection of an unresponsive "control" CEST agent that accounts for other conditions that influence CEST. The purpose of this study was to investigate the feasibility of in vivo catalyCEST MRI.
  
  
  METHODS
  CEST agents that were responsive and unresponsive to the activity of urokinase plasminogen activator were shown to have negligible interaction with each other. A CEST-fast imaging with steady state precession (FISP) MRI protocol was used to acquire MR CEST spectroscopic images with a Capan-2 pancreatic tumor model after intravenous injection of the CEST agents. A function of (super)-Lorentzian line shapes was fit to CEST spectra of a region-of-interest that represented the tumor.
  
  
  RESULTS
  The CEST effects from each agent showed the same initial uptake into tumor tissues, indicating that both agents had the same pharmacokinetic transport rates. Starting 5 min after injection, CEST from the enzyme-responsive agent disappeared more quickly than CEST from the unresponsive agent, indicating that the enzyme responsive agent was being catalyzed by urokinase plasminogen activator, while both agents also experienced net pharmacokinetic washout from the tumor.
  
  
  CONCLUSIONS
  CatalyCEST MRI demonstrates that dynamic tracking of enzyme-responsive and unresponsive CEST agents during the same in vivo MRI study is feasible.
authors: MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors: Byunghee
authors: B
authors: Yoo
authors: Vipul R
authors: VR
authors: Sheth
authors: Christine M
authors: CM
authors: Howison
authors: Matthew J K
authors: MJ
authors: Douglas
authors: Carlos T
authors: CT
authors: Pineda
authors: Erin A
authors: EA
authors: Maine
authors: Amanda F
authors: AF
authors: Baker
authors: Mark D
authors: MD
authors: Pagel
mesh_terms: D000818:Animals; D002384:Catalysis; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005240:Feasibility Studies; D006573:Heterocyclic Compounds, 1-Ring / Q000493:pharmacokinetics*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: D006573:Heterocyclic Compounds, 1-Ring; D019275:Radiopharmaceuticals; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D014568:Urokinase-Type Plasminogen Activator
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