Monitoring oxygenation during the growth of a transplanted tumor.

Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute, Department of Medicine, The Ohio State University, 420 West 12th Avenue, Room 114, Columbus, OH 43210, USA.
Advances in experimental medicine and biology (Impact Factor: 1.83). 02/2006; 578:375-80. DOI: 10.1007/0-387-29540-2_58
Source: PubMed
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    ABSTRACT: A novel procedure for in vivo imaging of the oxygen partial pressure (pO2) in implanted tumors is reported. The procedure uses electron paramagnetic resonance imaging (EPRI) of oxygen-sensing nanoprobes embedded in the tumor cells. Unlike existing methods of pO2 quantification, wherein the probes are physically inserted at the time of measurement, the new approach uses cells that are preinternalized (labeled) with the oxygen-sensing probes, which become permanently embedded in the developed tumor. Radiation-induced fibrosarcoma (RIF-1) cells, internalized with nanoprobes of lithium octa-n-butoxy-naphthalocyanine (LiNc-BuO), were allowed to grow as a solid tumor. In vivo imaging of the growing tumor showed a heterogeneous distribution of the spin probe, as well as oxygenation in the tumor volume. The pO2 images obtained after the tumors were exposed to a single dose of 30-Gy X-radiation showed marked redistribution as well as an overall increase in tissue oxygenation, with a maximum increase 6 hr after irradiation. However, larger tumors with a poorly perfused core showed no significant changes in oxygenation. In summary, the use of in vivo EPR technology with embedded oxygen-sensitive nanoprobes enabled noninvasive visualization of dynamic changes in the intracellular pO2 of growing and irradiated tumors.
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    ABSTRACT: Lithium naphthalocyanine (LiNc) is a crystalline material that has significant potential as a probe for EPR (electron paramagnetic resonance)-based biological oximetry (Pandian et al. J. Mater. Chem. 19:4138-4147, 2009a). However, implantation of LiNc crystals in tissues in raw or neat form is undesirable since dispersion of crystals in tissue may lead to loss of EPR signal, while also exacerbating biocompatibility concerns due to tissue exposure. To overcome these concerns, we have encapsulated LiNc crystals in an oxygen-permeable polymer, Teflon AF 2400 (TAF). Fabrication of TAF films incorporating LiNc particles (denoted as LiNc:TAF chip) was carried out using solvent-evaporation techniques. The EPR linewidth of LiNc:TAF chip was linearly dependent on oxygen-partial pressure (pO(2)) and did not change significantly relative to neat LiNc crystals. LiNc:TAF chip responded to changes in pO(2) reproducibly, enabling dynamic measurements of oxygenation in real time. The LiNc:TAF chips were stable in tissues for more than 2 months and were capable of providing repeated measurements of tissue oxygenation for extended periods of time. The results demonstrated that the newly fabricated, highly oxygen-sensitive LiNc:TAF chip will enhance the applicability of EPR oximetry for long-term and clinical applications.
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    ABSTRACT: Crystalline lithium phthalocyanine (LiPc) can be used to sense oxygen. To enhance biocompatibility/stability of LiPc, we encapsulated LiPc in Teflon AF (TAF), cellulose acetate (CA), and polyvinyl acetate (PVAc) (TAF, previously used to encapsulate LiPc, was a comparator). We identified water-miscible solvents that don't dissolve LiPc crystals, but are solvents for the polymers, and encapsulated crystals by solvent evaporation. Oxygen sensitivity of films was characterized in vitro and in vivo. Encapsulation did not change LiPc oximetry properties in vitro at anoxic conditions or varying partial pressures of oxygen (pO2). EPR linewidth of encapsulated particles was linear with pO2, responding to pO2 changes quickly and reproducibly for dynamic measurements. Encapsulated LiPc was unaffected by biological oxidoreductants, stable in vivo for four weeks. Oximetry, stability and biocompatibility properties of LiPc films were comparable, but both CA and PVAc films are cheaper, and easier to fabricate and handle than TAF films, making them superior.
    Biomedical Microdevices 01/2009; 11(2):379-87. · 2.72 Impact Factor