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Implicit and explicit dosimetry in photodynamic therapy: a New paradigm

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Abstract

Dosimetry for photodynamic therapy (PDT) is becoming increasingly complex as more factors are identified which may influence the effectiveness of a given treatment. The simple prescription of a PDT treatment in terms of the administered photosensitizer dose, the incident light and the drug-light time interval does not account for patient-to-patient variability in either the photosensitizer uptake, tissue optical properties or tissue oxygenation, nor for the interdependence of the photosensitizer-light-tissue factors. This interdependence is examined and the implications for developing adequate dosimetry for PDT are considered. The traditional dosimetric approach, measuring each dose factor independently, and termed here ‘explicit dosimetry’, may be contrasted with the recent trend to use photosensitizer photobleaching as an index of the effective delivered dose, termed here ‘implicit dosimetry’. The advantages and limitations of each approach are discussed, and the need to understand the degree to which the photobleaching mechanism is linked, or ‘coupled’, to the photosensitizing mechanism is analysed. Finally, the influence of the tissue-response endpoints on the optimal dosimetry methods is considered.

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References

  1. Dougherty TJ (ed). Photodynamic therapy.J. Clin Laser Med Surg 1996,14: 219–348

    Google Scholar 

  2. Fisher AMR, Murphree AL, Gomer CJ. Clinical and preclinical photodynamic therapy.Lasers Surg Med 1995,17: 2–31

    Article  CAS  PubMed  Google Scholar 

  3. Dougherty TJ. Photodynamic therapy.Photochem Photobiol 1993,58: 895–900

    Article  CAS  PubMed  Google Scholar 

  4. Fingar VH. Vascular effects of photodynamic therapy.J Clin Laser Surg Med 1996,14: 323–8

    CAS  Google Scholar 

  5. Braichotte DR, Savary J. F., Monnier P. et al. Optimizing light dosimetry in photodynamic therapy of early stage carcinoma of the esophagus using fluorescence spectroscopy.Lasers Surg Med 1996,19: 340–6

    Article  CAS  PubMed  Google Scholar 

  6. Braichotte DR, Wagnieres GA, Bays R. et al. Clinical pharmacokinetic studies of Photofrin by fluorescence spectroscopy in the oral cavity, the esophagus and the bronchi.Cancer 1995,75: 2768–78

    Article  CAS  PubMed  Google Scholar 

  7. Braichotte DR, Savary J-F, Glanzmann T. et al. Clinical pharmacokinetic studies of tetra (meta-hydroxyphenyl) chlorin in squamous cell carcinoma by fluorescence sectroscopy at 2 wavelengths.Int J Cancer 1995,63: 198–204

    Article  CAS  PubMed  Google Scholar 

  8. Wang I, Svanberg K, Andersson-Engels S et al. Photodynamic therapy of non-melanoma skin malignancies with topical amino levulinic acid: diagnostic measurements. In: Cortese DA (ed)5th International Photodynamic Association Biennial Meeting. Proc. SPIE, 1995,2371: 243–52

  9. Cheong WF, Prahl SA, Welch AJ. A review of the optical properties of biological tissues.IEEE J Quant Electr 1990,26: 2166–85

    Article  Google Scholar 

  10. Bays R, Wagnieres G, Robert D et al. Clinical measurements of tissue optical properties in the esophagus and in the oral cavity. In: Cortese DA (ed)5th International Photodynamic Association Biennial Meeting. Proc. SPIE, 1995,2371: 388–95

  11. Stone HB, Brown JM, Phillips TL et al. Oxygen in human tumors: Correlations between methods of measurement and response to therapy.Rad Res 1993,136: 422–34

    Article  CAS  Google Scholar 

  12. Chen Q., Wilson BC, Shetty S. et al. Changes inin vivo optical properties and light distributions in normal canine prostate during photodynamic therapy.Radiát Res 1997,147: 86–91

    Article  CAS  PubMed  Google Scholar 

  13. Van Geel IPJ, Oppelaar H., Oussoren YG, Stewart FA. Changes in perfusion of mouse tumours after photodynamic therapy.Int J Cancer 1994,56: 224–8

    Article  PubMed  Google Scholar 

  14. Wilson BC, Patterson MS, Burns DM. Effect of photosensitizer concentration in tissue on the penetration depth of photoactivating light.Lasers Med Sci 1986,1: 235–44

    Article  Google Scholar 

  15. Potter WR. PDT dosimetry and response. In: Dougherty TJ (ed)Photodynamic Therapy: Mechanisms. Proc. SPIE, 1989,1065: 88–99

  16. Stringer MR, Robinson DJ, Hudson EJ et al.In uivo monitoring of photosensitizer fluorescence during photodynamic therapy. In: Cortese DA (ed)5th International Photodynamic Association Biennial Meeting. Proc. SPIE, 1995,2371: 104–108

  17. Svaasand LO, Potter WR. The implications of photobleaching for photodynamic therapy. In: Henderson BW, Dougherty TJ (eds.)Photodynamic Therapy New York: Marcel Dekker Inc, 1992; Chap 23, pp. 369–85

    Google Scholar 

  18. Foster TH, Gao L. Dosimetry in photodynamic therapy: oxygen and the critical importance of capillary density.Radiat Res 1992,130: 379–83

    Article  CAS  PubMed  Google Scholar 

  19. Foster TH, Nichols MG. Oxygen sensitivity of PDT determined from time-dependent electrode measurements in spheroids. In: Dougherty TJ (ed)Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy IV. Proc. SPIE, 1995,2392: 141–51

  20. Grossweiner LI. Photodynamic therapy. In:The Science of Phototherapy Boca Raton: CRC Press, 1994; Chap 8, pp. 139–55

    Google Scholar 

  21. Patterson MS, Wilson BC. A theoretical study of the influence of sensitizer photobleaching on depth of necrosis in photodynamic therapy. In: Dougherty TJ (ed)Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy III. Proc. SPIE, 1994,2133: 208–19

  22. Sterenborg HJCM, van Gemert MJC. Photodynamic therapy with pulsed light sources: A theoretical analysis.Phys Med Biol 1996,41: 835–49

    Article  CAS  PubMed  Google Scholar 

  23. Wilson BC, Jeeves WP, Lowe D.In uivo andpost mortem measurements of the attenuation spectra of light in tissues.Photochem Photobiol 1985,42: 153–62

    Article  CAS  PubMed  Google Scholar 

  24. Jacques SL. Tissue fluorescence. In: Cortese DA (ed)5th International Photodynamic Association Biennial Meeting. Proc. SPIE, 1995,2371: 2–13

  25. Star WM, Wilson BC, Patterson MS. Light delivery and optical dosimetry in photodynamic therapy of solid tumors. In: Henderson BW, Dougherty TJ (eds.)Photodynamic Therapy New York: Marcel Dekker Inc, 1992; Chap 22, pp. 335–68

    Google Scholar 

  26. Pandey RK, Potter WR, Meunier I. et al. Evaluation ofnew benzoporphyrin derivatives with enhanced PDT activity.Photochem Photobiol 1995,62: 764–8

    Article  CAS  PubMed  Google Scholar 

  27. Patterson MS, Hayward JE, Farrell TF, Wilson BC. A general purpose instrument for PDT dosimetry. In: Cortese DA (ed)5th International Photodynamic Association Biennial Meeting. Proc. SPIE, 1995,2371: 477–81

  28. Jones LR, Grossweiner LI. Effects of Photofrin on in vivo skin reflectivity.J Photochem Photobiol 1996,B33: 153–6

    Google Scholar 

  29. Vaupel P., Schlenger K., Knoop C. et al. Oxygenation of human tumors: Evaluation of tissue oxygen distribution in breast cancers by computerized O2 tension measurements.Cancer Res 1991,51: 3316–22

    CAS  PubMed  Google Scholar 

  30. Vinogradov SA, Lo L-W, Jenkins WT et al. Noninvasive imaging of the distribution of oxygen in tissuein vivo using near-infrared phosphors.Biophys J. 1996,70: 1609–17

    Article  CAS  PubMed  Google Scholar 

  31. Patterson MS, Wilson BC, Graff R.In vivo tests of the concept of photodynamic threshold dose in normal rat liver photosensitized by aluminum chlorosulphonated phthalocyanine.Photochem Photobiol 1990,51: 343–9

    Article  CAS  PubMed  Google Scholar 

  32. Lilge L., Olivo MC, Schatz SW et al. The sensitivity of normal brain and intracranially implanted VX2 tumour to interstitial photodynamic therapy.Br J Cancer 1996,73: 332–43

    CAS  PubMed  Google Scholar 

  33. Chen Q., Chopp M., Madigan L. et al. Damage threshold of normal rat brain in photodynamic therapy.Photochem Photobiol 1996,64: 163–7

    Article  CAS  PubMed  Google Scholar 

  34. Messmann H, Mlkvy P, Davies C et al. Threshold effects of PDT in the normal rat colon with ALA photosensitization. In: Cortese DA (ed)5th International Photodynamic Association Biennial Meeting. Proc. SPIE, 1995,2371: 532–535

  35. Foster TH, Murant RS, Bryant RG et al. Oxygen consumption and diffusion effects in photodynamic therapy.Radiat Res 1991,126: 296–303

    Article  CAS  PubMed  Google Scholar 

  36. Foster TH, Hartley DF, Nichols MG et al. Fluence rate effects in photodynamic therapy of multicell tumor spheroids.Cancer Res 1993,53: 1249–54

    CAS  PubMed  Google Scholar 

  37. Wilson BC. Optical and photobiological dosimetry for photodynamic therapy of solid tumors. In: Dewey WC et al (eds.)Radiation Research, A Twentieth Century Perspective. New York: Academic Press, 1992: 674–9

    Google Scholar 

  38. Potter WR, Bellnier DA, Pandy R, Parsons JC, Dougherty TJ. Sensitizer pharmacokinetics byin vivo reflectance spectroscopy.Photochem Photobiol 1997 (in press)

  39. Bezdetnaya L., Zeghari N., Belitchenko I. et al. Spectroscopic and biological testing of photobleaching of porphyrins in solution.Photochem Photobiol 1996,64: 382–6

    Article  CAS  PubMed  Google Scholar 

  40. Georgakoudi I., Nichols MG, Foster TH. The mechanism of Photofrin photobleaching and its consequences for photodynamic therapy.Photochem Photobiol 1997,65: 135–44

    Article  CAS  PubMed  Google Scholar 

  41. Jacques SL, Joseph R, Gofstein G. How photobleaching affects dosimetry and fluorescence monitoring of PDT in turbid media. In: Dougherty TJ (ed)Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy II. Proc. SPIE, 1881: 168–79

  42. Sinaasappel M., Sterenborg HJCM. Quantification of hematoporphyrin derivative by fluorescence measurement using dual wavelength excitation and dual wavelength detection.Appl Opt 1993,32: 541–8

    Article  CAS  Google Scholar 

  43. Chen J-Y, Chen W., Chai H-X, Dong R-C. Studies on pharmacokinetics of sulfonated aluminum phthalocyanine in a transplantable mouse tumor byin vivo fluorescence.J Photochem Photobiol 1993,B18: 233–7

    Google Scholar 

  44. Jacques SL, Rodriguez T, Schwartz J. Kinetics of ALAinduced protoporphyrin IX accumulation in the liver, skin and tumor of a rat model. In: Dougherty TJ (ed)Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy IV. Proc. SPIE, 1995,2392: 8–12

  45. Katsumi T, Aizawa K, Kuroiwa Y et al. Effectiveness of photodynamic therapy with a diode laser used mono-Laspartyl chlorin e6 for implanted fibrosarcoma in mice. In: Cortese DA (ed)5th International Photodynamic Association Biennial Meeting. Proc. SPIE, 1995,2371: 86–9

  46. Glanzmann T, Theumann J-F, Forrer M et al. Evaluation of mTHPC of “early” squamous cell carcinomas of the cheek pouch mucosa of Golden Syrian hamsters as a model for clinical PDT of “early” cancers in the upper aerodigestive tract, the esophagus and the tracheo-bronchial tree. In: Cortese DA (ed)5th International Photodynamic Association Biennial Meeting. Proc. SPIE, 1995,2371: 51–8

  47. Andersson-Engels S., Berg R., Svanberg K. et al. Multicolour fluorescence imaging in connection with photodynamic therapy of 8-amino levulinic acid (ALA) sensitised skin malignancies.Bioimaging 1995,3: 134–43

    Article  Google Scholar 

  48. Moan J. Effect of bleaching of porphyrin sensitizers during photodynamic therapy.Cancer Lett 1986,33: 45–53

    Article  CAS  PubMed  Google Scholar 

  49. Forrer M, Glanzman T, Braichotte D et al.In vivo measurement of fluorescence bleaching of meso-tetra hydroxy phenyl chlorin (mTHPC) in the esophagus and oral cavity. In: Cubeddu R, Mordon SR, Svanberg K (eds)Optical Biopsies. Proc. SPIE, 1995,2627: 1–7

  50. Rhodes LE, Tsoukas M., Anderson RR et al. A quantitative model for ALA pharmacokinetics and phototoxicity using iontophoretic delivery of ALA.Photochem Photobiol 1996,63: 90S, abstract

    Google Scholar 

  51. Georgakoudi I., Foster TH. Photobleaching of PpIX, NBSe and NBS during photodynamic therapy (PDT) of multicell tumor spheroids.Photochem Photobiol 1996,63: 90S, abstract

    Google Scholar 

  52. Cubeddu R., Canti G, Musolino M et al.In vivo absorption spectrum of disulphonated aluminium phthalocyanine in a murine tumour model.J Photochem Photobiol 1996,B34: 229–35

    Google Scholar 

  53. Star WM.In vivo action spectra, absorption and fluorescence excitation spectra of photosensitizers for photodynamic therapy.J Photochem Photobiol 1995,B28: 101–2

    Google Scholar 

  54. van der Veen N, van Leengoed HLLM, Star WM.In vivo fluorescence kinetics and photodynamic therapy using 5-aminolaevulinic acid-induced porphyrin: increased damage after multiple irradiations.Br J Cancer 1994,70: 867–72

    PubMed  Google Scholar 

  55. Gudgin Dickson EF, Pottier RH. On the role of protoporphyrin IX photoproducts in photodynamic therapy.J Photochem Photobiol 1995,B29: 91–3

    Google Scholar 

  56. Rotomskis R, Bagdonas S, Streckyte G. Spectroscopic studies of photobleaching and photoproduct formation of porphyrins used in tumour therapy.J Photochem Photobiol 1996,B33: 61–7

    Google Scholar 

  57. Moan J, Kessel D. Photoproducts formed from Photofrin II in cells.J Photochem Photobiol 1988,Bl: 429–36

    Google Scholar 

  58. Patterson MS, Madsen SJ, Wilson BC. Experimental tests of the feasibility of singlet oxygen luminescence monitoringin vivo during photodynamic therapy.J Photochem Photobiol 1990,B5: 69–84

    Google Scholar 

  59. Moan J. On the diffusion length of singlet oxygen in cells and tissues.J Photochem Photobiol 1990,B6: 343–7

    Google Scholar 

  60. Hudson E, Stringer M, Scholfield J et al. Measurement of the photodynamic dose in an optical phantom. In: Cortese DA (ed)5th International Photodynamic Association Biennial Meeting. Proc. SPIE, 1995,2371: 159–163

  61. Pogue BW, Llige L, Patterson MS et al. The absorbed photodynamic dose examined from pulsed and CW light using tissue-simulating dosimeters.Appl Opt 1997 (in press)

  62. Aveline BM, Hasan T, Remond RW. The effects of aggregation, protein binding and cellular incorporation on the photophysical properties of benzoporphyrin derivative monoacid ring A (BPDMA).J Photochem Photobiol 1995,B30: 161–9

    Google Scholar 

  63. Smith G, McGimpsey WG, Lynch MC et al. An efficient oxygen independent two-photon photosensitization mechanism.Photochem Photobiol 1994,59: 135–9

    Article  CAS  PubMed  Google Scholar 

  64. Sanghvi NT, Hynynen K, Lizzi FL. New developments in therapeutic ultrasound.IEEE Eng Med Biol 1996, Nov/Dec: 83–92

  65. Yeung WTI, Lee T-Y, Del Maestro RF et al.In vivo CT measurement of blood-brain transfer constant of iopamidol in human brain tumors.J Neuro-Oncol 1992,14: 177–87

    CAS  Google Scholar 

  66. Yeung I, Lilge L, Wilson BC. Photodynamic therapy (PDT) induced alterations of blood-brain-barrier transfer constant of a tracer molecule in normal brain. In: Dougherty TJ (ed)Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy VI. Proc. SPIE, 1997,2972: 54–63

  67. Dodd NJF, Moore JV, Poppitt DG et al.In vivo magnetic resonance imaging of the effects of photodynamic therapy.Br J Cancer 1989,60: 164–7

    CAS  PubMed  Google Scholar 

  68. van Geel IPJ, Oppelaar H, Oussoren YG et al. Mechanisms for optimising photodynamic therapy: secondgeneration photosensitizers in combination with mitomycin CBr J Cancer 1995,72: 344–50

    PubMed  Google Scholar 

  69. Mordon S, Devoisselle JM, Maunoury V.In vivo measurement and imaging of tumor tissue using a pH-sensitive fluorescent probe (5,6-carboxyfluorescein): instrumental and experimental studies.Photochem Photobiol 1994,60: 274–9

    Article  CAS  PubMed  Google Scholar 

  70. Fingar VH, Henderson BW. Drug and light dose dependence of photodynamic therapy: a study of tumor and normal tissue response.Photochem Photobiol 1987,46: 837–41

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Ontario Cancer Institute, Toronto, Ontario, Canada

    B. C. Wilson

  2. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

    B. C. Wilson & L. Lilge

  3. Ontario Laser and Lightwave Research Centre, Toronto, Ontario, Canada

    B. C. Wilson & L. Lilge

  4. Hamilton Regional Cancer Center and Departments of Radiology and Physics, McMaster University, Hamilton,Ontario, Canada

    M. S. Patterson

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  1. B. C. Wilson
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  2. M. S. Patterson
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  3. L. Lilge
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Wilson, B.C., Patterson, M.S. & Lilge, L. Implicit and explicit dosimetry in photodynamic therapy: a New paradigm. Laser Med Sci 12, 182–199 (1997). https://doi.org/10.1007/BF02765099

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  • DOI: https://doi.org/10.1007/BF02765099

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