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Sensing and Imaging Molecular Oxygen in Mammals with Spin Lattice Relaxation Electron Paramagnetic Resonance

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Abstract

Molecular oxygen and its thermodynamic transformation drive nearly all life processes. Quantitative measurement and imaging of oxygen in living systems is of fundamental importance for the study of life processes and their aberrations—disease– many of which are affected by hypoxia, or low levels of oxygen. Cancer is among the disease processes profoundly affected by hypoxia. Electron paramagnetic resonance has been shown to provide remarkably accurate images of normal and cancerous tissue. In this review, we emphasize the reactivity of molecular oxygen particularly highlighting the metabolic processes of living systems to store free energy in the reactants. The history of hypoxic resistance of living systems to cytotoxic therapy, particularly radiation therapy is also reviewed. The measurement and imaging of molecular oxygen with pulse spin lattice relaxation (SLR) electron paramagnetic resonance (EPR) is reviewed briefly. This emphasizes the advantages of the spin lattice relaxation based measurement paradigm to reduce the sensitivity of the measurement to the presence of the oxygen sensing probe itself. The involvement of a novel small mammal external beam radiation delivery system is described. This enables an experimental paradigm based on control by radiation of the last resistant clonogen. This is much more specific for tumor cure than growth delay assays which primarily reflects control of tumor cells most sensitive to therapy.

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Funding

National Institutes of Health grants P41 EB002034, R01 CA098575, R01 CA236385, R50 CA211408, P30 CA014599, T32 EB002103, R44 CA224840, and F31 CA254223.

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Authors and Affiliations

  1. Department of Radiation and Cellular Oncology, The University of Chicago Medical Center MC1105, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA

    Howard J. Halpern

  2. Center for EPR Imaging In Vivo Physiology, The University of Chicago Medical Center MC1105, 5841 S. Maryland Avenue, Chicago, IL, 60637, USA

    Howard J. Halpern

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  1. Howard J. Halpern
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Correspondence to Howard J. Halpern.

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Conflicts of interest

The author reports US patents 8,664,955B1, 2020026098A1, 20160324438A1 and 9,392,957B1 for aspects of the pO2 imaging technology. The author is a member of O2M Technologies, Inc.

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Halpern, H.J. Sensing and Imaging Molecular Oxygen in Mammals with Spin Lattice Relaxation Electron Paramagnetic Resonance. Mol Imaging Biol (2024). https://doi.org/10.1007/s11307-024-01908-y

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