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Direct and Continuous Measurements of Oxygen Partial Pressure Using a Tissue-Inserted Optical Oxygen Microsensor: During Photodynamic Therapy

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Novel Approaches in Biosensors and Rapid Diagnostic Assays
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Abstract

Photodynamic Therapy (PDT) is an anti-cancer treatment modality in which sensitizer drug, light and oxygen are used to photochemically cause cell death. The cytotoxicity of PDT is based on the toxic effects of singlet oxygen and other free radicals generated by the photosensitizer in target cells upon illumination. Successful application of anticancer therapy and especially PDT depends on oxygen content within the tumor. Application of an optical oxygen microsensor allowed continuous and direct in situ measurements of temporal variations in the oxygen partial pressure (pO2) during PDT. The oxygen microsensor, developed by us in collaboration with OST, Israel, is an on-line system based on fluorescence measurements that provides continuous monitoring of blood and tissue oxygen levels. This study examined the spatial and temporal variations in the concentration of oxygen within solid tumors, during PDT. We found that illumination of Bacteriochlorophyll-Serine (a sensitizer drug) treated tumors leads to a rapid decline in tissue oxygen. Analysis of the process permitted a detailed description of the dynamics of oxygen depletion and reoxygenation. Moreover, it was shown that tumor oxygen tension becomes irreversibly low as a result of the effect of PDT. These results were interpreted in terms of vasculature damage. Magnetic resonance imaging studies confirmed the above findings and clearly showed that PDT induces vascular damage. Integration of the sensor in PDT experiments enables the in vivo analysis of the basic mechanisms underlying photoinduced cytotoxicity as well as the development of treatment protocols that optimize the synchronization of light pulses with tissue reoxygenation.

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References

  1. Dougherty TJ 1992, Photochemistry in the treatment of cancer, Adv. Photochem. 17:275-311.

    Article  CAS  Google Scholar 

  2. Foote CS, 1987;. Light activated pesticides. American Chem. Soc. Symposium Ser.1:22-38.

    Google Scholar 

  3. Keene JP, Kessel D, Land EJ, Redmond RW, Truscott TG, 1986, Direct detection of singlet oxygen sensitized by haematoporphyrin and related compounds. Photochem.Photobiol. 43:117-20.

    Article  CAS  Google Scholar 

  4. Weishaupt KR, Gomer CJ, Dougherty TJ, 1976, Identification of singlet oxygen as the cytotoxic agent in photoinactivation of amurine tumor. Cancer. Res. 36:2326-29.

    CAS  Google Scholar 

  5. Henderson BW, Dougherty TJ,I99, How does photodynamic therapy work? Photochem. Photobiol. 55:145-57.

    Google Scholar 

  6. Vaupel P, Schlenger K, Knoop C, Hockel M.,1991, Oxygenation of human tumors: evaluation of tissue oxygen distribution in breast cancers by computerized 02 tension measurements. Cancer. Res. 51:3316-22.

    CAS  Google Scholar 

  7. Lartigau E, Vitu L, Haie MC, 1992, Feasibility of measuring oxygen tension in uterine cervix carcinoma. Eur. J. Cancer.28a. 1353-57.

    Google Scholar 

  8. Hirst DG, 1989, Tumor hypoxia implication for therapy. Int. J.Radiat. Biol. 56:207-213.

    Article  Google Scholar 

  9. Foster TH, Murant RS, Bryant RG, Knox RS, Gibson SL, Hilf R, 1991, Oxygen consumption and diffusion effects in photodynamic therapy. Radiat. Res. 126:296-303.

    Article  CAS  Google Scholar 

  10. Henning JP, Fournier RL, Hampton JA,I995, A transient mathematical model of oxygen depletion during photodynamic therapy. Radiat. Res. 142:221-6.

    Article  CAS  Google Scholar 

  11. Bromberg A, Zilberstein J, Riesemberg S, et al., 1996, Optical fiber sensors for blood gases and pH, based on porous glass tips. Sensor and Actuators B:. 31.

    Google Scholar 

  12. Scherz A, Salomon Y, Fiedor L, 1994, Scherz, A., Salomon, Y. &Fiedor, L.(1994b). Preparation of chlorophyll conjugates and their application as photosensitizers in photodynamic therapy and general diagnostics. YEDA, Weizmann Institute of Science, European published patent application No.EP0584552.

    Google Scholar 

  13. Scherz A, Salomon Y, Fiedor L, 1994, Preparation of chlorophyll conjugates and their application as photosensitizers in photodynamic therapy and general diagnostics. YEDA, Weizmann Institute of Science, European published patent application No. EP0584552.

    Google Scholar 

  14. Gerst JE, Sole J, Mather JP, Salomon Y, 1986, Regulation of adenylate cyclase by ß-melanotropin in M2R melanoma cell line. Mol. Cell. Endocrinol. 46:137-147.

    Article  CAS  Google Scholar 

  15. Brezis M, Heyman SN, Epstein FH, 1994, Determinants of intrarenal oxygenation. II. Hemodynamic effects. Am. J. Physiol. 267:F1063-68.

    CAS  Google Scholar 

  16. Brezis M, Agmon Y, Epstein FH., 1994, Determinants of intrarenal oxygenation. I. Effects of diuretics. Am. J. Physiol. 267:f 1059-62.

    CAS  Google Scholar 

  17. Dewhirst MW, Ong ET, Klitzman B, et al., 1992, Perivascular oxygen tensions in a transplantable mammary tumor growing in a dorsal flap window chamber. Radiat.Res. 130:171-82.

    Article  CAS  Google Scholar 

  18. Gatenby RA, Kessler HB, Rosenblum JS, et al., 1988, Oxygen distribution ins quamous cell carcinoma metastases and its relationship to outcome of radiation therapy. Int. J. Radiat. Oncol. Biol. Phys. 14:831-8.

    Article  CAS  Google Scholar 

  19. Gustafsson U, Sjoberg F, Lewis DH, Thorborg P, 1994, Effect of hypoxic hypoxia and ritanserin on capillary flow and oxygenation in rabbit skeletal muscle. Acta.Physiol. Scand. 150:39-45.

    Article  CAS  Google Scholar 

  20. Harrison DK, Kessler M, Knauf SK, 1990, Regulation of capillary blood flow and oxygen supply in skeletal muscle in dogs during hypoxaemia. J. Physiol (Lond).420:431-446.

    CAS  Google Scholar 

  21. Khandelwal SR, Randad RS, Lin PS, et al., 1993, Enhanced oxygenation in vivo by allosteric inhibitors of hemoglobin saturation. Am. J. Physiol. 265 :H 1450-53.

    CAS  Google Scholar 

  22. Pappova N, Siracka E, Vacek A, Durkovsky J, 1982, Oxygen tension and prediction of the radiation response. Polarographic study in human breast cancer. Neoplasma. 29:669-74.

    CAS  Google Scholar 

  23. DeJordy JO, Bendel P, Horowitz A, Salomon Y, Degani H, 1992, Correlation of MR Imaging and histologic findings in mouse melanoma. J. Magn. Reson. Imag. 2:695-700.

    Article  CAS  Google Scholar 

  24. Vaupel PW, 1994, Blood flow, oxygenation, tissue pH distribution, and bioenergeticstatus of tumors. Ernst Schering Research Foundation lectures. 23 :p. 79. Information & Standards Medical Publications: 13342 Berlin, (Issn 0940-9300).

    Google Scholar 

  25. Fiedor L, Gorman AA, Hamblett I, et al., 1993, A pulsed laser and pulse radiolysis study of amphiphilic chlorophyll derivatives with PDT activity toward malignant melanoma. Photochem. Photobiol. 58:506-511.

    Article  CAS  Google Scholar 

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Zilberstein, J., Salomon, Y., Scherz, A., Bromberg, A. (2000). Direct and Continuous Measurements of Oxygen Partial Pressure Using a Tissue-Inserted Optical Oxygen Microsensor: During Photodynamic Therapy. In: Liron, Z., Bromberg, A., Fisher, M. (eds) Novel Approaches in Biosensors and Rapid Diagnostic Assays. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1231-8_20

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  • DOI: https://doi.org/10.1007/978-1-4615-1231-8_20

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5452-9

  • Online ISBN: 978-1-4615-1231-8

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