In vivo 19F magnetic resonance spectroscopy and chemical shift imaging of tri-fluoro-nitroimidazole as a potential hypoxia reporter in solid tumors Journal Article
| Authors: | Procissi, D.; Claus, F.; Burgman, P.; Koziorowski, J.; Chapman, J. D.; Thakur, S. B.; Matei, C.; Ling, C. C.; Koutcher, J. A. |
| Article Title: | In vivo 19F magnetic resonance spectroscopy and chemical shift imaging of tri-fluoro-nitroimidazole as a potential hypoxia reporter in solid tumors |
| Abstract: | 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. © 2007 American Association for Cancer Research. |
| Keywords: | controlled study; unclassified drug; clinical feature; nonhuman; solid tumor; nuclear magnetic resonance imaging; magnetic resonance imaging; cancer diagnosis; mouse; animal; metabolism; animals; mice; animal experiment; animal model; in vivo study; in vitro study; pathology; hypoxia; diagnostic agent; breast tumor; prostate tumor; rat; tumor cell; radiopharmaceutical agent; drug derivative; neoplasms, experimental; magnetic resonance spectroscopy; nuclear magnetic resonance spectroscopy; cell hypoxia; misonidazole; experimental neoplasm; high performance liquid chromatography; chromatography, high pressure liquid; ex vivo study; proton nuclear magnetic resonance; fluorine radioisotopes; fluorine; 2 nitro alpha [(2,2,2 trifluoroethoxy)methyl]imidazole 1 ethanol; 1 (2 nitro 1 imidazoyl) 3 (2,2,2 trifluoroethoxy) 2 propanol; 1-(2-nitro-1-imidazoyl)-3-(2,2,2-trifluoroethoxy)-2-propanol; oxygen affinity; visibility |
| Journal Title: | Clinical Cancer Research |
| Volume: | 13 |
| Issue: | 12 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2007-06-15 |
| Start Page: | 3738 |
| End Page: | 3747 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-06-1563 |
| PUBMED: | 17575240 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 25" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Source: Scopus" |
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