In vivo 19F magnetic resonance spectroscopy and chemical shift imaging of tri-fluoro-nitroimidazole as a potential hypoxia reporter in solid tumors

Daniel Procissi*, Filip Claus, Paul Burgman, Jacek Koziorowski, J. Donald Chapman, Sunitha B. Thakur, Cornelia Matei, C. Clifton Ling, Jason A. Koutcher

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Purpose: 2-Nitro-α-[(2,2,2-trifluoroethoxy)methyl]-imidazole-1- ethanol (TF-MISO) was investigated as a potential noninvasive marker of tissue oxygen levels in tumors using 19F magnetic resonance spectroscopy (MRS) and 19F chemical shift imaging. Experimental Designs: 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 19F 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 19F 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 19F signal under conditions of maximum hypoxia. Late time point (>6 h) tumor tissue concentrations, as obtained from 19F 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.

Original languageEnglish (US)
Pages (from-to)3738-3747
Number of pages10
JournalClinical Cancer Research
Issue number12
StatePublished - Jun 15 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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