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Applied Optics

Applied Optics


  • Vol. 36, Iss. 28 — Oct. 1, 1997
  • pp: 7257–7269

Absorbed photodynamic dose from pulsed versus continuous wave light examined with tissue-simulating dosimeters

Brian W. Pogue, Lothar Lilge, Michael S. Patterson, Brian C. Wilson, and Tayyaba Hasan  »View Author Affiliations

Applied Optics, Vol. 36, Issue 28, pp. 7257-7269 (1997)

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A dosimetric system has been developed to measure the spatially resolved light dose absorbed by a photosensitizer in a tissue-simulating medium. These gelatin-based dosimeters had macroscopic optical scattering and absorption properties that are typical for homogeneous tissue and contained the photosensitizer benzoporphyrin derivative monoacid (BPD-MA). A reporter molecule, 2′7′-dichlorofluorescin diacetate (DCF-DA), served as an actinometer, which could be photosensitized by BPD-MA to generate a highly fluorescent photoproduct. The relative photosensitizing efficiencies of high-intensity pulsed and cw laser light were compared in these tissue-simulating dosimeters. These measurements demonstrate an increase in penetration for pulsed light as compared with cw light in the dosimeters. A numerical simulation of the light propagation based on optical diffusion theory was used along with the energy levels of the photosensitizer molecule to examine the mechanisms involved in the absorbed dose. The increased penetration of high-intensity pulsed light was due to a transient decrease in the absorption of the photosensitizer, resulting from saturation of the photosensitizer optical transitions. This study provides the first direct comparison of the photodynamic dose absorbed by a photosensitizer using both high-intensity pulsed and cw laser light in a tissue-simulating medium. These measurements demonstrate that a small increase in depth of treatment is possible with pulsed laser light as compared with cw laser light simply on the basis of the unique photochemistry of the photosensitizer. However, this effect still needs to be examined carefully in tumor tissue, where other biological or chemical effects may become significant.

© 1997 Optical Society of America

Original Manuscript: June 17, 1996
Revised Manuscript: October 28, 1996
Published: October 1, 1997

Brian W. Pogue, Lothar Lilge, Michael S. Patterson, Brian C. Wilson, and Tayyaba Hasan, "Absorbed photodynamic dose from pulsed versus continuous wave light examined with tissue-simulating dosimeters," Appl. Opt. 36, 7257-7269 (1997)

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  1. T. J. Dougherty, “Yearly review: photodynamic therapy,” Photochem. Photobiol. 58, 895–900 (1993). [CrossRef] [PubMed]
  2. R. van Hillegersberg, W. J. Kort, J. H. P. Wilson, “Current status of photodynamic therapy in oncology,” Drugs 48, 510–527 (1994). [CrossRef] [PubMed]
  3. C. J. Gomer, “Preclinical examination of first and second generation photosensitizers used in photodynamic therapy [review],” Photochem. Photobiol. 54, 1093–1107 (1991). [CrossRef] [PubMed]
  4. B. W. Henderson, T. J. Dougherty, “How does photodynamic therapy work?” Photochem. Photobiol. 55, 145–157 (1992). [CrossRef] [PubMed]
  5. D. Phillips, “The photochemistry of sensitizers for photodynamic therapy,” Pure Appl. Chem. 67, 117–126 (1995). [CrossRef]
  6. H. I. Pass, “Review: photodynamic therapy in oncology: mechanisms and clinical use,” J. Natl. Cancer Inst. 85, 443–456 (1993). [CrossRef] [PubMed]
  7. J. G. Levy, “Recent clinical results with benzoporphyrin derivative monoacid ring A,” presented at Twenty-third Annual meeting of the American Society of Photobiology, Washington, D.C. (May 1995).
  8. T. Hasan, J. A. Parrish, “Photodynamic therapy of cancer,” in Cancer Medicine (Williams and Wilkins, Baltimore, Md., 1996), Chap. 50, pp. 739–751.
  9. B. C. Wilson, M. S. Patterson, “The physics of photodynamic therapy,” Phys. Med. Biol. 31, 327 (1986). [CrossRef] [PubMed]
  10. A. E. Profio, D. R. Doiron, “Dose measurements in photodynamic therapy of cancer,” Lasers Surg. Med. 7, 1–5 (1987). [CrossRef] [PubMed]
  11. J. L. Boulnois, “Photophysical processes in recent medical laser developments: a review,” Lasers Med. Sci. 1, 47–63 (1985). [CrossRef]
  12. A. R. Morgan, D. Skalkos, “Second generation photosensitizers: where are we going and where should we be going?” in Future Directions and Applications in Photodynamic Therapy, SPIE Inst. Series6, 87–106.
  13. S. G. Bown, C. J. Tralau, P. D. C. Smith, D. Akdemir, T. J. Weiman, “Photodynamic therapy with porphyrin and phthal ocyanine sensitization: quantitative studies in normal rat liver,” Br. J. Cancer 54, 43–52 (1986). [CrossRef] [PubMed]
  14. M. S. Patterson, B. C. Wilson, R. Graff, “In vivo tests of the concept of photodynamic threshold dose in normal rat liver photosensitized by aluminum chlorosulphonated phthalocyanine,” Photochem. Photobiol. 51, 343–349 (1990). [CrossRef] [PubMed]
  15. J. A. Barltrop, J. D. Coyle, Principles of Photochemistry (Wiley, Toronto, 1978), Chap. 3.
  16. T. Okunaka, H. Kato, C. Konaka, H. Sakai, H. Kawabe, K. Aizawa, “A comparison between argon-dye and excimer-dye laser for photodynamic effect in transplanted mouse tumor,” Jpn. J. Cancer Res. 83, 226–231 (1992). [CrossRef] [PubMed]
  17. M. S. Patterson, B. C. Wilson, “A theoretical study of the influence of sensitizer photobleaching on depth of necrosis in photodynamic therapy,” in Free-Space Laser Communication Technologies VI, G. Mecherle, ed., Proc. SPIE2133, 208–219 (1994).
  18. A. A. Andreoni, “Two-step photoactivation of hematoporphyrin by excimer-pumped dye-laser pulses,” J. Photochem. Photobiol. 1, 181–193 (1987). [CrossRef]
  19. G. Smith, W. G. McGimpsey, M. C. Lynch, I. E. Kochevar, R. W. Redmond, “An oxygen independent two-photon photosensitization mechanism,” Photochem. Photobiol. 59, 135–139 (1994). [CrossRef] [PubMed]
  20. P. Vaupel, F. Kallinowski, P. Okunieff, “Blood, flow oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review,” Cancer Res. 49, 6449–6465 (1989). [PubMed]
  21. H. Stiel, K. Teuchner, A. Paul, W. Freyer, D. Leupold, “Two-photon excitation of alkyl-substituted magnesium phthalocyanine: radical formation via higher excited states,” J. Photochem. Photobiol. 80, 289–298 (1994). [CrossRef]
  22. L. Lilge, T. J. Flotte, I. E. Kochevar, S. L. Jacques, F. Hillenkamp, “Photoactivable fluorophores for the measurement of fluence in turbid media,” Photochem. Photobiol. 58, 37–44 (1993). [CrossRef]
  23. L. W. Mason, A. J. Welch, M. J. C. van Gemert, “Photodynamic assay of light distributions in tissue phantoms,” Lasers Surg. Med. 8, 521–526 (1988). [CrossRef] [PubMed]
  24. A. S. Keston, R. Brandt, “The fluorometric analysis of ultramicro quantities of hydrogen peroxide,” Anal. Biochem. 11, 1–5 (1965). [CrossRef] [PubMed]
  25. J. A. Royall, H. Ischiropoulos, “Evaluation of 2′7′-dichlorofluorescin and dihydrorhodamine 123 as fluorescent probes for intracellular H2O2 in cultured endothelial cells,” Arch. Biochem. Biophys. 302, 348–355 (1993). [CrossRef] [PubMed]
  26. C. P. Label, H. Ischiropoulos, S. C. Bondy, “Evaluation of the probe 2′7′-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress,” Chem. Res. Toxicol. 5, 227–231 (1992). [CrossRef]
  27. P. E. Hockberger, M. S. Ahmed, C. Lee, T. A. Skimina, W. Y. Hung, T. Siddique, “Imaging of hydrogen peroxide in cultured cells using carboxy-dichlorofluorescein,” in Optical Diagnostics of Living Cells and Biofluids, D. L. Farkas, R. C. Leif, A. V. Priezzhev, T. Asakuru, B. J. Tromburg, eds., Proc. SPIE2678, 129–140.
  28. B. M. Aveline, T. Hasan, R. W. Redmond, “Photophysical and photosensitizing properties of benzoporphyrin derivative monoacid ring A (BPD-MA),” Photochem. Photobiol. 59, 328–335 (1994). [CrossRef] [PubMed]
  29. R. Gilles, N. Kollias, T. Hasan, H. Diddens, “Spectral characterization of the BPD-MA photoproduct formed in fetal calf solutions during irradiation with 690 nm cw radiation,” J. Photochem. Photobiol. 33, 87–90 (1996). [CrossRef]
  30. M. S. Patterson, S. Anderson-Engels, B. C. Wilson, “Absorption spectroscopy in tissue-simulating materials: a theoretical and experimental study of photon paths,” Appl. Opt. 34, 22–30 (1995). [CrossRef] [PubMed]
  31. S. J. Madsen, M. S. Patterson, B. C. Wilson, “The use of India ink as an optical absorber in tissue-simulating phantoms,” Phys. Med. Biol. 37, 985–993 (1992). [CrossRef] [PubMed]
  32. W. F. Cheong, S. A. Prahl, A. J. Welch, “A review of the optical properties of biological tissues,” IEEE J. Quantum Electron. 26, 2166–2185 (1990). [CrossRef]
  33. B. C. Wilson, T. J. Farrell, M. S. Patterson, “An optical fibre-based reflectance spectrometer for non-invasive investigation of photodynamic sensitizers in vivo,” in Future Directions and Photodynamic Therapy, C. J. Gomer, ed., SPIE Inst. Series6, 219–232 (1990).
  34. T. J. Farrell, M. S. Patterson, B. C. Wilson, “A diffusion theory model of spatially resolved, steady state reflectance for the noninvasive determination of tissue optical properties in vivo,” Med. Phys. 19, 879–888 (1992). [CrossRef]
  35. A. Ishimaru, “Diffusion of a pulse in densely distributed scatterers,” J. Opt. Soc. Am. 68, 1045–1049 (1978). [CrossRef]
  36. W. M. Star, J. P. A. Marijnissen, M. J. C. van Gemert, “Light dosimetry in optical phantoms and in tissues. I. Multiple flux and transport theory,” Phys. Med. Biol. 33, 437–454 (1988). [CrossRef] [PubMed]
  37. A. Ishimaru, “Diffusion of light in turbid media,” Appl. Opt. 28, 2210–2215 (1989). [CrossRef] [PubMed]
  38. W. H. Press, S. A. Teukolsky, W. T. Vetterling, B. P. Flannery, Numerical Recipes in Fortran, The Art of Scientific Computing, 2nd ed. (Cambridge U. Press, New York, 1992) Chap. 19.
  39. M. S. Patterson, B. Chance, B. C. Wilson, “Time resolved reflectance and transmittance for the noninvasive measurement of tissue optical properties,” Appl. Opt. 18, 3484–3488 (1989).
  40. B. W. Pogue, R. W. Redmond, T. Hasan, “Dosimetry for pulsed-laser photodynamic therapy,” in Laser-Tissue Interaction VII, S. L. Jacques, ed., Proc. SPIE2681, 130–139 (1996). [CrossRef]
  41. B. M. Aveline, T. Hasan, R. W. Redmond, “The effects of aggregation, protein binding and cellular incorporation on the photophysical properties of benzoporphyrin derivative monoacid ring A (BPD-MA),” J. Photochem. Photobiol. B 30, 161–169 (1995). [CrossRef] [PubMed]
  42. T. J. Farrell, B. C. Wilson, M. S. Patterson, R. Chow, “The dependence of photodynamic threshold dose on treatment parameters in normal rat liver in vivo,” in Optical Methods for Tumor Treatment and Early Diagnosis: Mechanisms and Techniques, T. J. Dougherty, ed., Proc. SPIE1426, 146–155 (1991). [CrossRef]
  43. M. C. Berenbaum, R. Bonnett, P. A. Scourides, “In vivo biological activity of the components of haematoporphyrin derivative.” Br. J. Cancer 45, 571–581 (1982). [CrossRef] [PubMed]
  44. J. C. van Gemert, M. C. Berenbaum, G. H. M. Gijsbers, “Wavelength and light-dose dependence in tumour phototherapy with haematoporphyrin derivative,” Br. J. Cancer 52, 43–49 (1985). [CrossRef] [PubMed]
  45. V. H. Fingar, W. R. Potter, B. W. Henderson, “Drug and light dose dependence of photodynamic therapy: a study of tumor cell clonogenicity and histologic changes,” Photochem. Photobiol. 45, 643–650 (1987). [CrossRef] [PubMed]
  46. B. C. Wilson, M. S. Patterson, D. M. Burns, “Effect of photosensitizer concentration in tissue on the penetration depth of photoactivating light,” Lasers Med. Sci. 1, 235–244 (1986). [CrossRef]
  47. C. J. Tralau, A. J. MacRobert, P. D. Coleridge-Smith, H. Barr, S. G. Bown, “Photodynamic therapy with phthalocyanine sensitization: quantitative studies in a transplantable rat fibrosarcoma,” Br. J. Cancer 55, 389–395 (1987). [CrossRef] [PubMed]

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