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In vivo electron paramagnetic resonance imaging of differential tumor targeting using cis ‐3,4‐di(acetoxymethoxycarbonyl)‐2,2,5,5‐tetramethyl‐1‐pyrrolidinyloxyl
Author(s) -
Redler Gage,
Barth Eugene D.,
Bauer Kenneth S.,
Kao Joseph P.Y.,
Rosen Gerald M.,
Halpern Howard J.
Publication year - 2014
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.24813
Subject(s) - nuclear magnetic resonance , electron paramagnetic resonance , in vivo , paramagnetism , magnetic resonance imaging , electron paramagnetic resonance spectroscopy , chemistry , materials science , physics , medicine , biology , radiology , condensed matter physics , microbiology and biotechnology
Purpose Electron paramagnetic resonance spectroscopy promises quantitative images of important physiologic markers of animal tumors and normal tissues, such as p O 2 , pH, and thiol redox status. These parameters of tissue function are conveniently reported by tailored nitroxides. For defining tumor physiology, it is vital that nitroxides are selectively localized in tumors relative to normal tissue. Furthermore, these paramagnetic species should be specifically taken up by cells of the tumor, thereby reporting on both the site of tumor formation and the physiological status of the tissue. This study investigates the tumor localization of the novel nitroxide, cis ‐3,4‐di(acetoxymethoxycarbonyl)‐2,2,5,5‐tetramethyl‐1‐pyrrolidin‐yloxyl 3 relative to the corresponding di‐acid 4 . Methods We obtained images of nitroxide 3 infused intravenously into C3H mice bearing 0.5‐cm 3 FSa fibrosarcoma on the leg, and compared these with images of similar tumors infused with nitroxide 4 . Results The ratio of spectral intensity from within the tumor‐bearing region to that of normal tissue was higher in the mice injected with 3 relative to 4 . Conclusion This establishes the possibility of tumor imaging with a nitroxide with intracellular distribution and provides the basis for EPR images of animal models to investigate the relationship between crucial aspects of tumor microenvironment and malignancy and its response to therapy. Magn Reson Med 71:1650–1656, 2014. © 2013 Wiley Periodicals, Inc.