Fabrication and physical evaluation of a polymer-encapsulated paramagnetic probe for biomedical oximetry

Meenakshisundaram, Guruguhan; Eteshola, Edward; Pandian, Ramasamy P.; Bratasz, Anna; Lee, Stephen C.; Kuppusamy, Periannan

doi:10.1007/s10544-009-9292-x

Cited by 38 publications

(45 citation statements)

References 29 publications

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“…A minor accumulation of red blood cells and some necrotic cells around the LiPc deposits is typically observed, which perhaps reflect the normal histological pattern of the tumor. In order to enhance the biocompatibility, in particularly for clinical applications, various encapsulations of the oximetry probes in biocompatible and inert polymers have been developed, which could be potentially retrieved after the treatments (Dinguizli et al, 2006; Meenakshisundaram et al, 2009a; Meenakshisundaram et al, 2009b). …”

Section: Methodsmentioning

confidence: 99%

Repeated assessment of orthotopic glioma pO2 by multi-site EPR oximetry: A technique with the potential to guide therapeutic optimization by repeated measurements of oxygen

Khan

Mupparaju

Hou

et al. 2012

Journal of Neuroscience Methods

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Tumor hypoxia plays a vital role in therapeutic resistance. Consequently, measurements of tumor pO2 could be used to optimize the outcome of oxygen-dependent therapies, such as, chemoradiation. However, the potential optimizations are restricted by the lack of methods to repeatedly and quantitatively assess tumor pO2 during therapies, particularly in gliomas. We describe the procedures for repeated measurements of orthotopic glioma pO2 by multi-site electron paramagnetic resonance (EPR) oximetry. This oximetry approach provides simultaneous measurements of pO2 at more than one site in the glioma and contralateral cerebral tissue. The pO2 of intracerebral 9L, C6, F98 and U251 tumors, as well as contralateral brain, were measured repeatedly for five consecutive days. The 9L glioma was well oxygenated with pO2 of 27 - 36 mm Hg, while C6, F98 and U251 glioma were hypoxic with pO2 of 7 - 12 mm Hg. The potential of multi-site EPR oximetry to assess temporal changes in tissue pO2 was investigated in rats breathing 100% O2. A significant increase in F98 tumor and contralateral brain pO2 was observed on day 1 and day 2, however, glioma oxygenation declined on subsequent days. In conclusion, EPR oximetry provides the capability to repeatedly assess temporal changes in orthotopic glioma pO2. This information could be used to test and optimize the methods being developed to modulate tumor hypoxia. Furthermore, EPR oximetry could be potentially used to enhance the outcome of chemoradiation by scheduling treatments at times of increase in glioma pO2.

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Section: Methodsmentioning

confidence: 99%

Repeated assessment of orthotopic glioma pO2 by multi-site EPR oximetry: A technique with the potential to guide therapeutic optimization by repeated measurements of oxygen

Khan

Mupparaju

Hou

et al. 2012

Journal of Neuroscience Methods

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“…Although we have alternative probes, based on lithium phthalocyanine (LiPc) derivatives [33, 47, 66] that are much superior to India ink in terms on oxygen sensitivity, and other desirable properties their use in human awaits regulatory approval. One important consideration towards increasing the safety of the implanted probe material, which is usually in the form of microcrystalline powder, is to encapsulate it in a biocompatible, oxygen-permeable polymer [54, 55, 67–69]. The encapsulation will not only hold the probe particulates from smearing or migration over a period of time but also avoid direct contact of the probe with the cells.…”

Section: Constraints For Clinical Epr Developmentmentioning

confidence: 99%

Clinical EPR

et al. 2014

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Electron paramagnetic resonance (EPR) spectroscopy has been well established as a viable technique for measurement of free radicals and oxygen in biological systems, from in vitro cellular systems to in vivo small animal models of disease. However, the use of EPR in human subjects in the clinical setting, although attractive for a variety of important applications such as oxygen measurement, is challenged with several factors including the need for instrumentation customized for human subjects, probe and regulatory constraints. This paper describes the rationale and development of the first clinical EPR systems for two important clinical applications, namely, measurement of tissue oxygen (oximetry), and radiation dose (dosimetry) in humans. The clinical spectrometers operate at 1.2 GHz frequency and use surface loop resonators capable of providing topical measurements up to 1 cm depth in tissues. Tissue pO2 measurements can be carried out noninvasively and repeatedly after placement of an oxygen-sensitive paramagnetic material (currently India ink) at the site of interest. Our EPR dosimetry system is capable of measuring radiation-induced free radicals in the tooth of irradiated human subjects to determine the exposure dose. These developments offer potential opportunities for clinical dosimetry and oximetry, which include guiding therapy for individual patients with tumors or vascular disease, by monitoring of tissue oxygenation. Further work is in progress to translate this unique technology to routine clinical practice.

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“…Therefore, we are developing an alternative approach for their clinical use. The raw particulates (of 10–100 µm size) are embedded in biocompatible materials that have high oxygen permeability [16, 17]. The probes are effectively shielded from interaction with the biological milieu that could result in biochemical degradation and breakdown, as well as limiting the probability of local and/or systemic toxicity effects from interactions of the probe with the tissues.…”

Section: Probes For Clinical Epr Oximetrymentioning

confidence: 99%

Advances in Probes and Methods for Clinical EPR Oximetry

Swartz¹,

Hou

Khan

et al. 2014

Advances in Experimental Medicine and Biology

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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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Fabrication and physical evaluation of a polymer-encapsulated paramagnetic probe for biomedical oximetry

Cited by 38 publications

References 29 publications

Repeated assessment of orthotopic glioma pO2 by multi-site EPR oximetry: A technique with the potential to guide therapeutic optimization by repeated measurements of oxygen

Repeated assessment of orthotopic glioma pO2 by multi-site EPR oximetry: A technique with the potential to guide therapeutic optimization by repeated measurements of oxygen

Clinical EPR

Advances in Probes and Methods for Clinical EPR Oximetry

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