title: In vivo 19F magnetic resonance spectroscopy and chemical shift imaging of tri-fluoro-nitroimidazole as a potential hypoxia reporter in solid tumors.
abstract: OBJECTIVE
  2-Nitro-alpha-[(2,2,2-trifluoroethoxy)methyl]-imidazole-1-ethanol (TF-MISO) was investigated as a potential noninvasive marker of tissue oxygen levels in tumors using (19)F magnetic resonance spectroscopy (MRS) and (19)F chemical shift imaging.
  
  
  METHODS
  In vitro data were obtained using high-performance liquid chromatography on tumor cells incubated under varying oxygen conditions to determine the oxygen-binding characteristics. In vivo data were obtained using a well-characterized hypoxic murine breast tumor (MCa), in addition to studies on a rat prostate tumor model (R3327-AT) implanted in nude mice. Detection of intratumor (19)F signal from TF-MISO was done using MRS for up to 10 h following a 75 mg/kg i.v. injection. Localized distribution of the compound in the implanted MCa tumor has been imaged using slice-selective two-dimensional chemical shift imaging 6 h after injection.
  
  
  RESULTS
  The in vitro results showed that TF-MISO preferentially accumulates in cells incubated under anoxic conditions. The in vivo (19)F MR spectral features (line width and chemical shift) were recorded as a function of time after injection, and the results indicate that the fluorine atoms are indeed sensitive to changes in the local environment while still providing a detectable MR signal. Ex vivo spectra were collected and established the visibility of the (19)F signal under conditions of maximum hypoxia. Late time point (>6 h) tumor tissue concentrations, as obtained from (19)F MRS, suggest that TF-MISO is reduced and retained in hypoxic tumor. The feasibility of obtaining TF-MISO tumor distribution maps in a reasonable time frame was established.
  
  
  CONCLUSIONS
  Based on the results presented herein, it is suggested that TF-MISO has the potential to be a valid magnetic resonance hypoxia imaging reporter for both preclinical hypoxia studies and hypoxia-directed clinical therapy.
authors.affiliation: Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. procissi@caltech.edu
authors.forename: Daniel
authors.initials: D
authors.lastname: Procissi
authors.forename: Filip
authors.initials: F
authors.lastname: Claus
authors.forename: Paul
authors.initials: P
authors.lastname: Burgman
authors.forename: Jacek
authors.initials: J
authors.lastname: Koziorowski
authors.forename: J Donald
authors.initials: JD
authors.lastname: Chapman
authors.forename: Sunitha B
authors.initials: SB
authors.lastname: Thakur
authors.forename: Cornelia
authors.initials: C
authors.lastname: Matei
authors.forename: C Clifton
authors.initials: CC
authors.lastname: Ling
authors.forename: Jason A
authors.initials: JA
authors.lastname: Koutcher
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002851:Chromatography, High Pressure Liquid; D005462:Fluorine Radioisotopes; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*
chemical_list: D005462:Fluorine Radioisotopes; C059168:1-(2-nitro-1-imidazoyl)-3-(2,2,2-trifluoroethoxy)-2-propanol; D008920:Misonidazole