In vivo topical EPR spectroscopy and imaging of nitroxide free radicals and polynitroxyl-albumin

Periannan Kuppusamy, Penghai Wang, Ravi A. Shankar, Li Ma, Charles E. Trimble, Carleton J.C. Hsia, Jay L. Zweier

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46 Scopus citations

Abstract

Piperidine nitroxides have considerable clinical potential, both as antioxidant therapeutic compounds and contrast agents in magnetic resonance imaging. However, their development has thus far been limited by their rapid bioreduction in vivo. Recently, it was reported that polynitroxyl albumin (PNA) can reverse the bioreduction of the reduced 4-hydroxy-2,2,6,6- tetramethylpiperidine-N-oxyl (Tempol) in the rat heart, enabling the performance of high resolution EPR imaging for prolonged time (Kuppusamy et al., Biochemistry 35, 7051-7057 (1996)). In this report, the efficacy of PNA in maintaining Tempol concentrations in vivo in mice was demonstrated, using L-band (1.25 GHz) EPR spectroscopy and imaging. The EPR signal of intravenous Tempol had a half-life of 1.0 ± 0.2 min and became undetectable within 6 min. Subcutaneous Tempol, however, decayed at a slower rate (half-life, 5.0 ± 0.5 min) suggesting that Tempol had been bioreduced to the corresponding hydroxylamine form, Tempol-H. Subcutaneously injected PNA restored 20% of the Tempol signal in the vicinity of the PNA deposit. In vivo topical EPR imaging demonstrated that the Tempol signal was restored at the site of PNA injection, but not at locations remote from the PNA injection site. The ability of PNA to maintain Tempol in its paramagnetic state in vivo should enable a wide range of therapeutic and diagnostic applications of piperidinyl nitroxides.

Original languageEnglish
Pages (from-to)806-811
Number of pages6
JournalMagnetic Resonance in Medicine
Volume40
Issue number6
DOIs
StatePublished - Dec 1998

Keywords

  • EPR imaging
  • Metabolism
  • Mice
  • Nitroxide
  • Skin

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