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In vivo topical EPR spectroscopy and imaging of nitroxide free radicals and polynitroxyl‐albumin
Author(s) -
Kuppusamy Periannan,
Wang Penghai,
Shankar Ravi A.,
Ma Li,
Trimble Charles E.,
Hsia Carleton J. C.,
Zweier Jay L.
Publication year - 1998
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.1910400604
Subject(s) - in vivo , electron paramagnetic resonance , chemistry , nitroxide mediated radical polymerization , nuclear magnetic resonance , radical , hydroxylamine , antioxidant , human serum albumin , biophysics , biochemistry , organic chemistry , physics , microbiology and biotechnology , radical polymerization , copolymer , biology , polymer
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. Subcutane‐ously 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.