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Advances in Probes and Methods for Clinical EPR Oximetry

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Oxygen Transport to Tissue XXXVI

Abstract

EPR oximetry, which enables reliable, accurate, and repeated measurements of the partial pressure of oxygen in tissues, provides a unique opportunity to investigate the role of oxygen in the pathogenesis and treatment of several diseases including cancer, stroke, and heart failure. Building on significant advances in the in vivo application of EPR oximetry for small animal models of disease, we are developing suitable probes and instrumentation required for use in human subjects. Our laboratory has established the feasibility of clinical EPR oximetry in cancer patients using India ink, the only material presently approved for clinical use. We now are developing the next generation of probes, which are both superior in terms of oxygen sensitivity and biocompatibility including an excellent safety profile for use in humans. Further advances include the development of implantable oxygen sensors linked to an external coupling loop for measurements of deep-tissue oxygenations at any depth, overcoming the current limitation of 10 mm. This paper presents an overview of recent developments in our ability to make meaningful measurements of oxygen partial pressures in human subjects under clinical settings.

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References

  1. Ahmad R, Kuppusamy P (2010) Theory, instrumentation, and applications of electron paramagnetic resonance oximetry. Chem Rev 110:3212–3236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Swartz HM, Khan N, Buckey J, Comi R, Gould L, Grinberg O, Hartford A, Hopf H, Hou H, Hug E, Iwasaki A, Lesniewski P, Salikhov I, Walczak T (2004) Clinical applications of EPR: overview and perspectives. NMR Biomed 17:335–351

    Article  CAS  PubMed  Google Scholar 

  3. Swartz HM, Walczak T (1998) Developing in vivo EPR oximetry for clinical use. Adv Exp Med Biol 454:243–252

    Article  CAS  PubMed  Google Scholar 

  4. Swartz HM, Liu KJ, Goda F, Walczak T (1994) India ink: a potential clinically applicable EPR oximetry probe. Magn Reson Med 31:229–232

    Article  CAS  PubMed  Google Scholar 

  5. Goda F, Liu KJ, Walczak T, O’Hara JA, Jiang J, Swartz HM (1995) In vivo oximetry using EPR and india ink. Magn Reson Med 33:237–245

    Article  CAS  PubMed  Google Scholar 

  6. Williams BB, Khan N, Zaki B, Hartford A, Ernstoff MS, Swartz HM (2010) Clinical electron paramagnetic resonance (EPR) oximetry using india ink. Adv Exp Med Biol 662:149–156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Liu KJ, Gast P, Moussavi M, Norby SW, Vahidi N, Walczak T, Wu M, Swartz HM (1993) Lithium phthalocyanine: a probe for electron paramagnetic resonance oximetry in viable biological systems. Proc Natl Acad Sci U S A 90:5438–5442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ilangovan G, Manivannan A, Li H, Yanagi H, Zweier JL, Kuppusamy P (2002) A naphthalocyanine-based EPR probe for localized measurements of tissue oxygenation. Free Radic Biol Med 32:139–147

    Article  CAS  PubMed  Google Scholar 

  9. Pandian RP, Parinandi NL, Ilangovan G, Zweier JL, Kuppusamy P (2003) Novel particulate spin probe for targeted determination of oxygen in cells and tissues. Free Radic Biol Med 35:1138–1148

    Article  CAS  PubMed  Google Scholar 

  10. Pandian RP, Dolgos M, Marginean C, Woodward PM, Hammel PC, Manoharan PT, Kuppusamy P (2009) Molecular packing and magnetic properties of lithium naphthalocyanine crystals: hollow channels enabling permeability and paramagnetic sensitivity to molecular oxygen. J Mater Chem 19:4138–4147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bratasz A, Pandian RP, Ilangovan G, Kuppusamy P (2006) Monitoring oxygenation during the growth of a transplanted tumor. Adv Exp Med Biol 578:375–380

    Article  PubMed  Google Scholar 

  12. Eubank TD, Roberts RD, Khan M, Curry JM, Nuovo GJ, Kuppusamy P, Marsh CB (2009) Granulocyte macrophage colony-stimulating factor inhibits breast cancer growth and metastasis by invoking an anti-angiogenic program in tumor-educated macrophages. Cancer Res 69:2133–2140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Khan M, Kutala VK, Vikram DS, Wisel S, Chacko SM, Kuppusamy ML, Mohan IK, Zweier JL, Kwiatkowski P, Kuppusamy P (2007) Skeletal myoblasts transplanted in the ischemic myocardium enhance in situ oxygenation and recovery of contractile function. Am J Physiol Heart Circ Physiol 293:H2129–H2139

    Article  CAS  PubMed  Google Scholar 

  14. Khan M, Meduru S, Mohan IK, Kuppusamy ML, Wisel S, Kulkarni A, Rivera BK, Hamlin RL, Kuppusamy P (2009) Hyperbaric oxygenation enhances transplanted cell graft and functional recovery in the infarct heart. J Mol Cell Cardiol 47:275–287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Selvendiran K, Bratasz A, Kuppusamy ML, Tazi MF, Rivera BK, Kuppusamy P (2009) Hypoxia induces chemoresistance in ovarian cancer cells by activation of signal transducer and activator of transcription 3. Int J Cancer 125:2198–2204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Meenakshisundaram G, Eteshola E, Pandian RP, Bratasz A, Lee SC, Kuppusamy P (2009) Fabrication and physical evaluation of a polymer-encapsulated paramagnetic probe for biomedical oximetry. Biomed Microdevices 11:773–782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Meenakshisundaram G, Pandian RP, Eteshola E, Lee SC, Kuppusamy P (2010) A paramagnetic implant containing lithium naphthalocyanine microcrystals for high-resolution biological oximetry. J Magn Reson 203:185–189

    Article  CAS  PubMed  Google Scholar 

  18. Meenakshisundaram G, Eteshola E, Pandian RP, Bratasz A, Selvendiran K, Lee SC, Krishna MC, Swartz HM, Kuppusamy P (2009) Oxygen sensitivity and biocompatibility of an implantable paramagnetic probe for repeated measurements of tissue oxygenation. Biomed Microdevices 11:817–826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hou H, Dong R, Li H, Williams B, Lariviere JP, Hekmatyar SK, Kauppinen RA, Khan N, Swartz H (2012) Dynamic changes in oxygenation of intracranial tumor and contralateral brain during tumor growth and carbogen breathing: a multisite EPR oximetry with implantable resonators. J Magn Reson 214:22–28

    Article  CAS  PubMed  Google Scholar 

  20. Hou H, Li H, Dong R, Mupparaju S, Khan N, Swartz H (2011) Cerebral oxygenation of the cortex and striatum following normobaric hyperoxia and mild hypoxia in rats by EPR oximetry using multi-probe implantable resonators. Adv Exp Med Biol 701:61–67

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Li H, Hou H, Sucheta A, Williams BB, Lariviere JP, Khan MN, Lesniewski PN, Gallez B, Swartz HM (2010) Implantable resonators: a technique for repeated measurement of oxygen at multiple deep sites with in vivo EPR. Adv Exp Med Biol 662:265–272

    Article  PubMed  PubMed Central  Google Scholar 

  22. Swartz HM, Williams BB, Zaki BI, Hartford AC, Jarvis LA, Chen EY, Comi RJ, Ernstoff MS, Hou H, Khan N, Swartz SG, Flood AB, Kuppusamy P (2013) Clinical EPR: unique opportunities and some challenges. Acad Radiol 21:197–206

    Article  Google Scholar 

  23. Vaupel P, Hockel M, Mayer A (2007) Detection and characterization of tumor hypoxia using pO2 histography. Antioxid Redox Signal 9:1221–1235

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The development and applications of EPR oximetry reported in this manuscript was supported by the following grants from the National Institutes of Health (NIH): P01 EB002180 (HMS), R21 CA121593 (HMS), R21DK072112 (NK), and R01 EB004031 (PK).

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Correspondence to Harold M. Swartz .

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Swartz, H.M. et al. (2014). Advances in Probes and Methods for Clinical EPR Oximetry. In: Swartz, H.M., Harrison, D.K., Bruley, D.F. (eds) Oxygen Transport to Tissue XXXVI. Advances in Experimental Medicine and Biology, vol 812. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0620-8_10

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