Abstract
Electron paramagnetic resonance imaging (EPRI) is a relatively recent imaging technique, which provides potentially multidimensional imaging of the spatial distribution of paramagnetic species. Thanks to the use of stable spin probes, low frequency EPR imaging has recently allowed the use of large tissue samples or whole animals in vivo in the field of biology and medicine. It is normally necessary to introduce prior intravenous or intramuscular infusion of stable or slowly metabolizable non-toxic water-soluble paramagnetic materials, or stable implantable particulate materials as spin probes into the system. The classification and research progress of spin probes at present were described briefly. Three important potential approaches in water-soluble paramagnetic materials design including deuterated, site-specific and macromolecular conjugated nitroxides were also investigated.
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Gallez B, Swartz H M. In vivo EPR: When, How and Why? NMR Biomed, 2004, 17: 223–225
Matsumoto K, Subramanian S, Murugesan R, et al. Spatially resolved biologic information from in vivo EPRI, OMRI, and MRI. Antioxid Redox Signal, 2007, 9: 1125–1141
Kuppusamy P, Zweier J L. Cardiac application of EPR imaging. NMR Biomed, 2004, 17: 226–239
Subramanian S, Matsumoto K I, Mitchell J B, et al. Radio frequency continuous-wave and time-domain EPR imaging and Overhauser-enhanced magnetic resonance imaging of small animals: instrumental developments and comparison of relative merits for functional imaging. NMR Biomed, 2004, 17: 263–294
Deng Y, He G, Petryakov S, et al. Fast EPR imaging at 300 MHz using spinning magnetic field gradients. J Magn Reson, 2004, 168: 220–227
Jackson S K, Madhani M, Thomas M, et al. Applications of in vivo electron paramagnetic resonance (EPR) spectroscopy: measurements of pO2 and NO in endotoxin shock. Toxicology Letters, 2001, 120: 253–257
Krishna M C, Devasahayam N, Cook J A, et al. Electron paramagnetic resonance for small animal imaging applications. ILAR Journal, 2001, 42(3): 209–218
Liebgott T, Li H, Deng Y, et al. Proton electron double resonance imaging (PEDRI) of the isolated beating rat heart. Magn Reson Med, 2003, 50: 391–399
Lurie D J, Davies G R, Foster M A, et al. Field-cycled PEDRI imaging of free radicals with detection at 450 mT. Magn Reson Imaging, 2005, 23: 175–181
Mailer C, Sundramoorthy S V, Pelizzari C A, et al. Spin echo spectroscopic electron paramagnetic resonance imaging. Magn Reson Med, 2006, 55: 904–912
Matsumoto S, Utsumi H, Aravalluvan T, et al. Influence of proton T1 on oxymetry using overhauser enhanced magnetic resonance imaging. Magn Reson Med, 2005, 54: 213–217
Modica A, Lurie D J, Alecci M. Sequential, co-registered fluorine and proton field-cycled overhauser imaging at a detection field of 59 mT. Phys Med Biol, 2006, 51: N39–N45
Berliner L J. In vivo EPR (ESR), Biological Magnetic Resonance, Vol 18, Kluwer Academic: New York, 2003
Swartz H M, Khan N, Buckey J, et al. Clinical applications of EPR: overview and perspectives. NMR Biomed, 2004, 17: 335–351
Nagano T, Yoshimura T. Bioimaging of Nitric oxide. Chem Rev, 2002, 102: 1235–1269
Novak I, Harrison L J, Kovac B, et al. Electronic structure of persistent radicals: nitroxide. J Org Chem, 2004, 69(22): 7628–7634
Kuppusamy P, Chzhan M, Wang P, et al. Electron paramagnetic resonance imaging of rat heart with nitroxide and polynitroxyl-albumin. Biochemistry, 1996, 35(22): 7051–7057
Kocherginsky N, Swartz H M. Terminology, Classification and Distribution of the Nitroxides in Cells. In Nitroxide Spin Labels: Reactions in Biology and Chemistry, Kocherginsky N, Swartz H M (eds). CRC Press: Boca Raton, FL, 1995, 15–26
Iannone A, Tomasi A, Quaresima V, et al. Nitroxides as metabolic and EPR imaging probes in biological model systems. Res Chem Intermed, 1993, 19: 715–731
Zweier J L, Chzhan M, Samouilov A, et al. Electron paramagnetic resonance imaging of the rat heart. Phys Med Biol, 1998, 43: 1823–1835
Kuppusamy P, Shankar R A, Zweier J L. In vivo measurement of arterial and venous oxygenation in the rat using 3D spectral-spatial electron paramagnetic resonance imaging. Phys Med Biol, 1998, 43: 1837–1844
Kotake Y, Oehler U M, Janzen E G. Two-dimensional ENDOR imaging based on differences in oxygen concentration. J Chem Soc, Faraday Trans 1, 1988, 84: 3275–3278
Sotgiu A, Colacicchi S, Placidi G, et al. Water soluble free radicals as biologically responsive agents in electron paramagnetic resonance imaging. Cell Mol Biol, 1997, 43: 813–823
Matsumoto K, Kawai S, Chignell C F, et al. Location of anthralin radical generation in mouse skin by UV-A irradiation: an estimation using microscopic EPR spectral-spatial imaging. Magn Reson Med, 2006, 55: 738–742
Li H, He G, Deng Y, et al. In vivo proton electron double resonance imaging of the distribution and clearance of nitroxide radicals in mice. Magn Reson Med, 2006, 55: 669–675
Matsumoto K, English S, Yoo J, et al. Pharmacokinetics of a triarylmethyl-type paramagnetic spin probe used in EPR oximetry. Magn Reson Med, 2004, 52: 885–892
Elas M, Williams B B, Parasca A, et al. Quantitative tumor oxymetric images from 4D electron paramagnetic resonance imaging (EPRI): methodology and comparison with blood oxygen leveldependent (BOLD) MRI. Magn Reson Med, 2003, 49(4): 682–691
Matsumoto K, Chandrika B, Lohman J A, et al. Application of continuous-wave EPR spectral-spatial image reconstruction techniques for in vivo oxymetry: comparison of projection reconstruction and constant-time modalities. Magn Reson Med, 2003, 50: 865–874
Smith C D. Synthesis and properties of novel free radicals with potential as molecular magnetic materials and spin probes. In: A Thesis Submitted for the Degree of Doctor of Philosophy, School of Physical and Chemical Sciences, Queensland University of Technology, 2002. 1–38
Micallef A S. Novel nitroxides and pronitroxides: synthesis and properties of new spin traps and spin probes with potential for biological application. In: A Thesis Submitted for the Degree of Doctor of Philosophy, School of Physical and Chemical Sciences, Queensland University of Technology, 2000. 1–43
Fuchs J, Groth N, Herrling T. Cutaneous tolerance to nitroxide free radicals in human skin. Free Radical Biol Med, 1998, 24(4): 643–648
Reid D A, Bottle S E, Micallef A S. The synthesis of water soluble isoindoline nitroxides and a pronitroxide hydroxylamine hydrochloride UV-VIS probe for free radicals. Chem Commun, 1998, 1907–1908
Karmarov A M, Joseph J, Lai C S. In vivo pharmacokinetics of nitroxides in mice. Biochem Biophys Res Commun, 1994, 201: 1035–1042
Grucker D, Guiberteau T, Eclancher B, et al. Dynamic nuclear polarization with nitroxides dissolved in biological fluids. J Magn Reson B, 1995, 106: 101–109
Guiberteau T, Grucker D, Dynamic nuclear polarization imaging in very low magnetic ields as a non invasive technique for oximetry. J Magn Reson, 1997, 124: 263–266
Mitchell J B, Russo A, Kuppusamy P, et al. Radiation, radicals, and images. Ann NY Acad Sci, 2000, 899: 28–43
Swartz H M. Principles of the metabolism of nitroxides and their implications for spin trapping. Free Radic Res Commun, 1990, 9: 399–405
Chen K, Glockner J F, Morse P D, et al. Effect of oxygen on the metabolism of nitroxide spin labels in cells. Biochemistry, 1989, 28: 2496–2501
Palas M A, Swartz H M. Oxygen dependent metabolism of potential magnetic resonance contrast agents. Invest Radiol, 1987, 22: 497–501
Swartz H M. Use of nitroxides to measure redox metabolis in cells and tissues. J Chem Soc, Faraday Trans, 1, 1987, 83:191–202
Swartz H M, Chen K, Pals M, et al. Hypoxia-sensitive NMR contrast agents. Magn Reson Med, 1986, 3: 169–174
Sotgiu A, Mader K, Placidi G, et al. pH-sensitive imaging by low frequency EPR: a model study for biological applications. Phys Med and Biol, 1998, 43: 1921–1930
Ferrari M, Quaresima V, Ursini C L, et al. In vivo electron paramagnetic resonance spectroscopy/imaging in experimental oncology: the hope and the reality. Int J Radiat Oncol Biol Phys, 1994, 29: 421–425
Gallez B, Debuyst H, Demeure R, et al. Evaluation of a nitroxyl fatty acid as liver contrast agent for magnetic resonance imaging. Magn Reson Med, 1993, 30: 592–599
Gallez B, Lacour V, Demeure R, et al. Spin labeled arabinogalactan as MRI contrast agent. Magn Reson Imag, 1994, 12: 61–69
Alecci M, Ferrari M, Quaresima V, et al. Simultaneous 280-MHz Epr imaging of rat organs during nitroxide free radical clearance. Biophys J, 1994, 67: 1274–1279
Kuppusamy P, Wang P, Zweier J L. Three-dimensional spatial EPR imaging of the rat heart. Magn Reson Med, 1995, 34: 99–105
Kuppusamy P, Chzhan M, Wang P, et al. Three-dimensional gated EPR imaging of the beating heart: time-resolved measurements of free radical distribution during the cardiac contractile cycle. Magn Reson Med, 1996, 35: 323–328
Stratford I J, Adams G E, Bremner J C, et al. Manipulation and exploitation of the tumour environment for therapeutic benefit. Int J Radiat Biol, 1994, 65: 85–94
Yoshimura T, Yokoyama H, Fujii S, et al. In vivo EPR detection and imaging of endogenous nitric oxide in lipopolysaccharide-treated mice. Nat Biotech, 1996, 14: 992–994
He G, Shankar R A, Chzhan M, et al. Noninvasive measurement of anatomic structure and intraluminal oxygenation in the gastrointestinal tract of living mice with spatial and spectral EPR imaging. Proc Natl Acad Sci USA, 1999, 96: 4586–4591
Yokoyama H, Itoh O, Aoyama M, et al. In vivo EPR imaging by using an acyl-protected hydroxylamine to analyze intracerebral oxidative stress in rats after epileptic seizures. Magn Reson Imag, 2000, 18: 875–887
Schafer F Q, Buettner G R. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med, 2001, 30: 1191–1212
Tada M, Yokoyama H A, Ito O, et al. Evaluation of the hepatic reduction of a nitroxide radical in rats receiving ascorbic acid, glutathione or ascorbic acid oxidase by in vivo electron spin resonance study. J Gast Hepat, 2004, 19: 99–105
Kuppusamy P, Krishna M C. EPR imaging of tissue redox status. Current Topic Biophys, 2002, 26(1): 29–34
Russo A, Carmichael J, Friedman N, et al. The roles of intracellular glutathione in antineoplastic chemotherapy. Int J Radiat Oncol Biol Phys, 1986, 12: 1347–1354
Mitchell J B, Russo A. The role of glutathione in radiation and drug induced cytotoxicity. Br J Cancer Suppl, 1987, 8: 96–104
Yu N Y, Brown J M. Depletion of glutathione in vivo as a method of improving the therapeutic ratio of misonidazole and SR 2508. Int J Radiat Oncol Biol Phys, 1984, 10: 1265–1269
Belton P S, Sutcliffe L H, Gillies D G, et al. A new water-soluble and lipid-insoluble spin probe: application to the study of aqueous sucrose solutions. Magn Reson Chem, 1999, 37: 36–42
Bottle S E, Chand U, Micallef A S. Hydrogen abstraction from unactivated hydrocarbons using a photochemically excited isoindoline nitroxide. Chem Lett, 1997, 9: 857–858
Micallef A S, Bott R C, Bottle S E, et al. Brominated isodolines: precursors to functionalized nitroxides. J Chem Soc Perkin Trans, 1999, 2: 65–71
Smith C D, Bott R C, Bottle S E, et al. New isodoline aminoxyl based polyradicals for spin probes and molecular magnetic materials. J Chem Soc Perkin Trans, 2002, 2: 533–537
Shen J, Bottle S E, Khan N, et al. Development of isoindoline nitroxides for EPR oximetry in viable systems. Appl Magn Reson, 2002, 22: 357–368
Gallez B, Baudelet C, Jordan B F. Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications. NMR Biomed, 2004, 17: 240–262
Utsumi H, Yamada K, Ichikawa K, et al. Simultaneous molecular imaging of redox reactions monitored by overhauser-enhanced MRI with 14N- and 15N-labeled nitroxyl radicals. Proc Natl Acad Sci USA, 2006, 103: 1463–1468
Gallez B, Bacic G, Goda F, et al. Use of nitroxides for assessing perfusion, oxygenation, and viability of tissues: in vivo EPR and MRI studies. Magn Reson Med, 1996, 35: 97–106
Swartz H M, Glockner J F. Measurement of oxygen by EPRI and EPRS. In EPR Imaging and in vivo EPR, Eaton G R, Eaton S S, Ohno K (eds). CRC Press: Boca Raton, FL, 1991, 261–290
Halpern H J, Yu C, Peric M, et al. Oxymetry deep in tissues with low-frequency electron paramagnetic resonance. Proc Natl Acad Sci U S A, 1994, 91: 13047–13051
Kuppusamy P, Wang P, Zweier J L. Three-dimensional spatial EPR imaging of the rat heart. Magn Reson Med, 1995, 34: 99–105
Ferrari M, Colacicchi S, Gualtieri G, et al. Whole mouse nitroxide free radical pharmacokinetics by low frequency electron paramagnetic resonance. Biochem Biophys Res Commun, 1990, 166: 168–173
Liu S M, Timmins G S, Shi H L, et al. Application of in vivo EPR in brain research: monitoring tissue oxygenation, blood flow, and oxidative stress. NMR Biomed, 2004, 17: 327–334
Gallez B, Bacic G, Dunn J, et al. Use of nitroxides for assessing perfusion, oxygenation, and viability of tissues: in vivo EPR and MRI studies. Magn Reson Med, 1996, 35: 97–106
Matsumoto K, Subramanian S, Devasahayam N, et al. Electron paramagnetic resonance imaging of tumor hypoxia: enhanced spatial and temporal resolution for in vivo pO2 determination. Magn Reson Med, 2006, 55: 1157–1163
Matsumoto K, Hyodo F, Matsumoto A, et al. High resolution mapping of tumor redox status by magnetic resonance imaging using nitroxides as redox-sensitive contrast agents. Clin Cancer Res, 2006, 12: 2455–2462
Matsumoto K, Bernardo M, Subramanian S, et al. MR assessment of changes of tumor in response to hyperbaric oxygen treatment. Magn Reson Med, 2006, 56: 240–246
Nelson J A, Schmiedl U. Porphyrins as contrast media. Magn Reson Med, 1991, 22: 366–371
Luo Y, Mei E W, Zhuo R X. Studies on water-soluble metalloporphyrins as tumor targeting magnetic resonance imaging contrast agents. Chem J Chin Univ, 1995, 16(10): 1629–1636
Yan G P, Bischa D, Bottle S E. Synthesis and properties of novel porphyrin spin probes containing isoindoline nitroxides. Free Radic Biol Med, 2007, 43(1): 111–116
Mader K. Pharmaceutical applications of in vivo EPR. Phys Med Biol, 1998, 43: 1931–1935
Berengian A R, Bova M P, Mchaourab H S. Structure and function of the conserved domain in A-crystallin. Site-directed spin labeling identifies a β-strand near a subunit interface. Biochemistry, 1997, 36: 9951–9957
Mchaourab H S, Oh K J, Fang C J, et al. The conformation of T4 lysozyme in solution. Hinge bending motion and the substrate-induced conformational transition studied by site-directed spin labeling. Biochemistry, 1997, 36: 307–316
Mchaourab H S, Berengian A, Koteiche H A. Site-directed spin-labeling study of the structure and subunit interactions along a conserved sequence in the a-crystallin domain of heat-shock protein 27. Evidence of a conserved subunit α interface. Biochemistry, 1997, 36: 14627–14634
Hubbell W L, Mchaourab H S, Altenbach C, et al. Watching proteins move using site-directed spin labeling. Structure, 1996, 4(7): 779–783
Steinhoff H J, Radzwill N, Thevis N, et al. Determination of interspin distances between spin labels attached to insulin: comparison of electron paramagnetic resonance data with X-ray structure. Biophys J, 1997, 73: 3287–3298
Gibney B R, Johansson J S, Rabanal F, et al. Global topology & stability and local structure & dynamics in a synthetic spin-labeled four-helix bundle protein. Biochemistry, 1997, 36(10): 2798–2806
Rein D A. Functionalised isoindoline, dibenzoisoindoline and imidazoisoindoline nitroxides: novel profluorescent and spin probes with diagnostic and therapeutic potential. In: A Thesis Submitted for the Degree of Doctor of Philosophy, School of Physical and Chemical Sciences, Queensland University of Technology, 2005, 1–44
Hustedt E J, Kirchner J J, Spaltenstein A, et al. Monitoring DNA dynamics using spin-labels with different independent mobilities. Biochemistry, 1995, 34(13): 4369–4375
Miller T R, Alley S C, Reese A W, et al. A probe for sequence-dependent nucleic acid dynamics. J Am Chem Soc, 1995, 117: 9377–9378
Okonogi T M, Reese A W, Alley S C, et al. Flexibility of duplex DNA on the sub-microsecond timescale. Biophys J, 1999, 77: 3256–3276
Gallez B, Bacic G, Goda F, et al. Use of nitroxides for assessing perfusion, oxygenation, and viability of tissues: in vivo EPR and MRI studies. Magn Reson Med, 1996, 35: 97–106
Glockner J F, Chan H C, Swartz H M. In vivo oximetry using a nitroxide-liposome system. Magn Reson Med, 1991, 20: 123–133
Di Giulio A, Carnicelli V, Colacicchi S, et al. An EPR study of lipid vesicle as contrast agent vectors. Appl Magn Reson, 1997, 13: 553–559
Demsar F, Kveder M, Rugelj S, et al. Hydroxylamines as oxygen-sensitive procontrast agents for in vivo magnetic resonance imaging. J Magn Reson, 1991, 95: 281–285
Towner R A, Zhdanov R I, Janzen E G. Use of nitroxides as MRI contrast agents to study in vivo carbon tetrachoride induced hepatotoxicity in rats. Free Radic Res Commun, 1993, 19: S211–S218
Liu K J, Grinstaff M W, Jiang J, et al. in vivo measurement of oxygen concentration using sonochemically synthesized microspheres. Biophys J, 1994, 67: 896–901
Matsumoto K, Yahiro T, Yamada K, et al. in vivo EPR spectroscopic imaging for a liposomal drug delivery system. Magn Reson Med, 2005, 53: 1158–1165
Ishida T, Shinozuka K, Kubota M, et al. Fullerene spin label synthesis and characterization of the [60]fullerene-substituted TEMPO radical. J Chem Soc Commun, 1995, 1841–1842
Arena F, Bullo F, Conti F, et al. Synthesis and EPR studies of radicals and biradical anions of C60 nitroxide derivatives. J Am Chem Soc, 1997, 119: 789–795
Kalina O, Tumanskii B. Paramagnetic fullerene derivative with an unpaired electron on the added moiety. In: Radical Reactions of fullerene and their derivatives. Dordrecht: Springer, 2001, 133–137
Medintz I L, Uyeda H T, Goldman E R. Quantum dot bioconjugates for imaging, labelling and sensing. Nat Mater, 2005, 4(6): 435–446
Michalet X, Pinaud F F, Bentolila L A. Quantum dots for liver cells, in vivo imaging, and diagnostics. Science, 2005, 307(5709): 538–544
Mulder W J, Koole R J. Quantum dots with a bimodal molecular imaging probe. Nano Lett, 2006, 6(1): 1–6
Gallani J L, Bonomme L, Drury A, et al. Photosensitive magnetism of radicals coupled with carbon nanotubes. Organic Electronics, 2003, 4: 15–20
Heald C G R, Wildgoose G G., Jiang L, et al. Chemical derivatisation of multiwalled carbon nanotubes using diazonium salts. Chem Phys Chem, 2004, 5: 1794–1799
Qin S H, Qin D Q, Ford W T, et al. Covalent cross-linked polymer/single-wall carbon nanotube multilayer films. Chem Mater, 2005, 17: 2131–2135
Dyke C A, Tour J M. Overcoming the insolubility of carbon nanotubes through high degrees of sidewall functionalization. Chem Eur J, 2004, 10: 812–817
Quaresima V, Alecci M, Ferrari M, et al. Whole rat electron paramagnetic resonance imaging of a nitroxide free radical by a radio frequency (280 MHz) spectrometer. Biochem Biophys Res Commun, 1992, 183: 829–835
Foster M A, Seimenis I, Lurie D J. The Application of PEDRI to the Study of Free Radicals in vivo. Phys Med Biol, 1998, 43: 1893–1897
Nicholson I, Robb F J L, McCallum S J, et al. Recent developments in combining LODESR imaging with proton NMR imaging. Phys Med Biol, 1998, 43: 1851–1855
McCallum S J, Nicholson I, Lurie D J. Multimodality magnetic resonance systems for studying free radicals in vivo. Phys Med Biol, 1998, 43: 1857–1861
Alecci M, Seimenis I, McCallum S J, et al. Nitroxide free radical clearance in the live rat monitored by radio-frequency CW-EPR and PEDRI. Phys Med Biol, 1998, 43: 1899–1905
Mader K. Pharmaceutical applications of in vivo EPR. Phys Med Biol, 1998, 43: 1931–1935
Quaresima V, Ferrari M. Current status of electron spin resonance (ESR) for in vivo detection of free radicals. Phys Med Biol, 1998, 43: 1937–1947
Sutcliffe L H. The design of spin probes for electron magnetic resonance spectroscopy and imaging. Phys Med Biol, 1998, 43: 1987–1993
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Supported by National Natural Science Foundation of China (Grant No. 50773060), Hubei Provincial International Project for Science and Technology Cooperation (Grant No. 2007CA015), Hubei Provincial Key Technologies Research and Development Program (Grant No. 2007AA301B24) and 2007 Endeavour Research Award of the Australian Government (Grant ERF-PDR-194-2007)
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Yan, G., Peng, L., Jian, S. et al. Spin probes for electron paramagnetic resonance imaging. Chin. Sci. Bull. 53, 3777–3789 (2008). https://doi.org/10.1007/s11434-008-0520-1
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DOI: https://doi.org/10.1007/s11434-008-0520-1