, Volume 48, Issue 4, pp 510–527 | Cite as

Current Status of Photodynamic Therapy in Oncology

  • Richard van Hillegersberg
  • Will J. Kort
  • J. H. Paul Wilson
Review Article


Photodynamic therapy (PDT) is a cancer treatment based on the accumulation in malignant tissue of a photosensitiser with low systemic toxicity. Subsequent illumination induces a type II photochemical reaction with singlet oxygen production that results in destruction of biomolecules and subcellular organelles.

The first full clinical report of PDT dates from 1976. Haematoporphyrin derivative, a complex mixture of porphyrins, was initially used as a photosensitiser. An enriched fraction (porfimer sodium) is now the most commonly used clinical agent. After systemic administration porphyrins bind to albumin and lipoproteins. Accumulation occurs mainly in tumours and organs of the reticuloendothelial system. The light of an argon-dye laser can be tuned to the appropriate wavelength and delivered either superficially, interstitially or intraluminally. Light distribution can be assessed by using a radiation transport model and tissue optical properties, or direct measurement with light detectors.

The effects of PDT depend in a complex way on: characteristics, tissue concentration and localisation of the photosensitiser; the target tissue optical properties and oxygenation; activation wavelength, power density and treatment regimen. Future research is directed towards: better photosensitisers (i.e. phthalocyanines, chlorins or protoporphyrin IX endogenously produced from 5-aminolevulinic acid); improved light generation and delivery; and combination with hyperthermia, chemotherapy, radiotherapy or surgery. Adjuvant intraoperative PDT is a promising approach to destroying residual tumour after surgery.


Porphyrin Photodynamic Therapy Photofrin Hematoporphyrin Derivative Haematoporphyrin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Raab O. Über die Wirkung fluoreszierender Stoffe auf Infusoria. Z Biol 1900; 39: 524–6Google Scholar
  2. 2.
    Tappeiner HV, Jesionek A. Therapeutische Versuche mit fluoreszierenden Stoffe. Muench Med Wochenschr 1903; 47: 2042–4Google Scholar
  3. 3.
    Meyer-Betz F. Untersuchungen über die biologische (photodynamische) Wirkung des Hematoporphyrins und andere Derivate des Bluts und Gallenfarbstoffs. Arch Dtsch Klin Med 1913; 112: 476–503Google Scholar
  4. 4.
    Auler H, Banzer G. Untersuchungen über die Rolle der Porphyrine bei geschwulstkranke Menschen und Tieren. Z Krebsforsch. 1942; 53: 65–8Google Scholar
  5. 5.
    Figge FHJ, Weiland GS, Manganiello LOJ. Cancer detection and therapy: affinity of neoplastic, embryonic and traumatized tissues for porphyrins and metalloporphyrins. Roy Soc Exp Biol Med 1948; 68: 640–1Google Scholar
  6. 6.
    Schwartz S, Absolon K, Vermund H. Some relationships of porphyrins, x-rays, and tumors. Univ Minnesota Med Bull 1955; 7: 7–13Google Scholar
  7. 7.
    Lipson RL, Blades EJ, Olsen AM. The use of hematoporphyrin in tumour destruction. J Natl Cancer Inst 1961; 26: 1–11PubMedGoogle Scholar
  8. 8.
    Diamond I, Granelli SG, McDonagh AF, et al. Photodynamic therapy of malignant tumors. Lancet 1972; 2: 1175–7PubMedGoogle Scholar
  9. 9.
    Dougherty TJ, Grindey GB, Fiel R, et al. Photoradiation therapy II: cure of animal tumors with hematoporphyrin and light. J Natl Cancer Inst 1975; 55: 115–21PubMedGoogle Scholar
  10. 10.
    Kelly JF, Snell ME. Hematoporphyrin derivative: a possible aid in the diagnosis and therapy of carcinoma of the bladder. J Urol 1976; 155: 150–1Google Scholar
  11. 11.
    Dougherty TJ. Photodynamic therapy (PDT) of malignant tumors. Crit Rev Oncol Hematol 1984; 2: 83–116PubMedGoogle Scholar
  12. 12.
    Dougherty TJ, Potter WR, Weishaupt KR. The structure of the active component of hematoporphyrin derivative. Prog Clin Biol Res 1984; 170: 301–14PubMedGoogle Scholar
  13. 13.
    Dougherty TJ, Marcus SL. Photodynamic therapy. Eur J Cancer 1992; 28A: 1734–42PubMedGoogle Scholar
  14. 14.
    Dougherty TJ. Studies on the structure of porphyrins contained in Photofrin® II. Photochem Photobiol 1987a; 46: 569–73PubMedGoogle Scholar
  15. 15.
    Kessel D, Thompson P, Musselman B, et al. Probing the structure and stability of the tumor localizing derivative of hematoporphyrin by reduction with LiAlH4. Cancer Res 1987; 47: 4642–5PubMedGoogle Scholar
  16. 16.
    Dougherty TJ. Photodynamic therapy: new approaches. Semin Surg Oncol 1989; 5: 6–16PubMedGoogle Scholar
  17. 17.
    Dougherty TJ. Photosensitization of malignant tumors. Semin Surg Oncol 1986; 2: 24–37PubMedGoogle Scholar
  18. 18.
    Razum N, Balchum OJ, Profio AE, et al. Skin photosensitivity: duration and intensity following intravenous hematoporphyrin derivatives, HpD, and DHE. Photochem Photobiol 1987; 46: 925–8PubMedGoogle Scholar
  19. 19.
    Dougherty TJ, Cooper MT, Mang TS. Cutaneous phototoxic occurrences in patients receiving photofrin. Lasers Surg Med 1990; 10: 485–8PubMedGoogle Scholar
  20. 20.
    Bellnier DA, Ho YK, Pandey RK, et al. Distribution and elimination of Photofrin® II in mice. Photochem Photobiol 1989; 50: 221–8PubMedGoogle Scholar
  21. 21.
    Jori G. Photodynamic therapy of solid tumors. Radiat Phys Chem 1987; 30: 375–80Google Scholar
  22. 22.
    Dougherty TJ. Photosensitizers: therapy and detection of malignant tumors. Photochem Photobiol 1987; 45: 879–89PubMedGoogle Scholar
  23. 23.
    Jori G, Reddi E. The role of lipoproteins in the delivery of tumour-targeting photosensitizers. Int J Biochem 1993; 25: 1369–75PubMedGoogle Scholar
  24. 24.
    Jori G. In vivo transport and pharmacokinetic behavior of tumour photosensitizers. Ciba Found Symp 1989; 146: 78–94PubMedGoogle Scholar
  25. 25.
    Korbelik M, Hung J. Cellular delivery and retention of Photofrin®: II. The effects of interaction with human plasma proteins. Photochem Photobiol 1991; 53: 501–10PubMedGoogle Scholar
  26. 26.
    Jori G, Beltramini M, Reddi E, et al. Evidence for a major role of plasma proteins as hematoporphyrin carriers in vivo. Cancer Lett 1984; 24: 291–7PubMedGoogle Scholar
  27. 27.
    Kessel D. Porphyrin lipoprotein association as a factor in porphyrin localization. Cancer Lett 1986; 33: 183–8PubMedGoogle Scholar
  28. 28.
    Gomer CJ, Dougherty TJ. Determination of (3H)- and (14C) hematoporphyrin derivative distribution in malignant and normal tissue. Cancer Res 1979; 39: 146–51PubMedGoogle Scholar
  29. 29.
    Bugelski PJ, Porter CW, Dougherty TJ. Autoradiographic distribution of hematoporphyrin derivative in normal and tumour tissue of the mouse. Cancer Res 1981; 41: 4606–12PubMedGoogle Scholar
  30. 30.
    Wilson BC, Van Lier. Radiolabelled photosensitizers for tumor imaging and photodynamic therapy. J Photochem Photobiol B 1989; 3: 459–63PubMedGoogle Scholar
  31. 31.
    Spikes JD, Jori G. Photodynamic therapy of tumours and other diseases. Lasers Med Sci 1987; 2: 3–15Google Scholar
  32. 32.
    Kessel D, Woodburn K. Biodistribution of photosensitizing agents. Int J Biochem 1993; 25: 1377–83PubMedGoogle Scholar
  33. 33.
    Wilson JHP, Van Hillegersberg R, Van den Berg JWO, et al. Photodynamic therapy for gastrointestinal tumors. Scand J Gastroenterol 1991; 188 Suppl. 26: 20–5Google Scholar
  34. 34.
    Wilson BC. Photodynamic therapy: light delivery and dosage for second-generation photosensitizers. Ciba Found Symp 1989; 146: 60–77PubMedGoogle Scholar
  35. 35.
    Bonnet R, Berenbaum M. Porhpyrins as photosensitizers. Ciba Found Symp 1989; 146: 40–59Google Scholar
  36. 36.
    Van Gemert MJC, Berenbaum MC, Gijsberts GHM. Wavelength and light-dose dependence in tumour phototherapy with hematoporphyrin derivative. Br J Cancer1985; 52: 43–9PubMedGoogle Scholar
  37. 37.
    Wilson BC, Jeeves WP, Lowe DM. In vivo and post-mortem measurements of the attenuation spectra of light in mammalian tissues. Photochem Photobiol1985; 2: 153–62Google Scholar
  38. 38.
    Gomer CJ, Doiron DR, Rucker N, et al. Action spectrum (620-640 nm) for hematoporphyrin derivative induced cell killing. Photochem Photobiol1984; 39: 365–8PubMedGoogle Scholar
  39. 39.
    Star WM, Versteeg J, Van Putten W, et al. Wavelength dependence of hematoporphyrin derivative photodynamic treatment on rat ears. Photochem Photobiol1990; 52: 547–54PubMedGoogle Scholar
  40. 40.
    Weishaupt KR, Gomer CJ, Dougherty TJ. Identification of singlet oxygen as the cytotoxic agent in photoactivation of a murine tumour. Cancer Res1976; 36: 2326–9PubMedGoogle Scholar
  41. 41.
    Gomer CJ, Razum NJ. Acute skin response in albino mice following porphyrin photosensitization under oxic and anoxic conditions. Photochem Photobiol1984; 40: 435–9PubMedGoogle Scholar
  42. 42.
    Mitchell JB, McPhearson S, DeGraff W, et al. Oxygen dependence of hematoporphyrin derivative induced photoinactivation of Chinese Hamster cells. Cancer Res1985; 45: 2008–11PubMedGoogle Scholar
  43. 43.
    Moan J, Sommer S. Oxygen dependence of the photosensitizing effect of hematoporphyrin derivative in NHIK-3025 cells. Cancer Res1985; 45: 1608–10PubMedGoogle Scholar
  44. 44.
    Henderson BW, Fingar VH. Oxygen limitation of direct tumour cell kill during photodynamic treatment of a murine tumour model. Photochem Photobiol1989; 49: 299–304PubMedGoogle Scholar
  45. 45.
    Chapman JD, Stobbe CC, Arnfield MR, et al. Oxygen dependency of tumor cell killing in vitro by light-activated Photofrin® II. Radiat Res1991; 126: 73–9PubMedGoogle Scholar
  46. 46.
    Valenzo DP. Photomodification of biological membranes with emphasis on singlet oxygen mechanisms. Photochem Photobiol1987; 46: 147–60Google Scholar
  47. 47.
    Foote CS. Definition of type I and type II photosensitized oxidation. Photochem Photobiol1991; 54: 659PubMedGoogle Scholar
  48. 48.
    Gomer CJ. Photodynamic therapy in the treatment of malignancies. Semin Hematol1989; 26: 27–34PubMedGoogle Scholar
  49. 49.
    Buettner GR, Need MJ. Hydrogen peroxide and hydroxyl free radical production by hematoporphyrin derivative, ascorbate and light. Cancer Lett 1985; 25: 297–304PubMedGoogle Scholar
  50. 50.
    Van Steveninck J, Tijssen K, Boegheim JP, et al. Photodynamic generation of hydroxyl radicals by hematoporphyrin derivative and light. Photochem Photobiol 1986; 44: 711–6PubMedGoogle Scholar
  51. 51.
    Athar MCA, Elmets DR, Bickers DR, et al. A novel mechanism for generation of Superoxide anions in hematoporphyrin derivative-mediated cutaneous photosensitization: activation of the xanthine oxidase pathway. J Clin Invest 1989; 83: 1137–43PubMedGoogle Scholar
  52. 52.
    Mang TS, Dougherty TJ, Potter WR, et al. Photobleaching of porphyrins used in photodynamic therapy and implications for therapy. Photochem Photobiol 1987; 45: 501–6PubMedGoogle Scholar
  53. 53.
    Potter WR, Mang TS, Dougherty TJ. The theory of photodynamic dosimetry: consequences of photodestruction of sensitizers. Photochem Photobiol 1987; 46: 97–101PubMedGoogle Scholar
  54. 54.
    Boyle DG, Potter WR. Photobleaching of photofrin II as a means of eliminating skin photosensitivity. Photochem Photobiol 1987; 46: 997–1001PubMedGoogle Scholar
  55. 55.
    Zhou C. Mechanisms of tumor necrosis induced by photodynamic therapy. J Photochem Photobiol 1989; 3: 299–318Google Scholar
  56. 56.
    Moan J, Berg K, Kvam E, et al. Intracellular localization of photosensitizers. Ciba Found Symp 1989; 146: 95–111PubMedGoogle Scholar
  57. 57.
    Jori G. Photosensitized processes in-vivo: proposed phototherapeutic applications. Photochem Photobiol 1990; 52: 439–43PubMedGoogle Scholar
  58. 58.
    Girotti AW. Photodynamic lipid peroxidation in biological systems. Photochem Photobiol 1990; 51: 497–509PubMedGoogle Scholar
  59. 59.
    Okunaka T, Eckhauser ML, Kato H, et al. Correlation between photodynamic efficacy of differing porphyrins and membrane partitioning behavior. Lasers Surg Med 1992; 12: 98–103PubMedGoogle Scholar
  60. 60.
    Kessel D. Sites of photosensitization by derivates of hematoporphyrin. Photochem Photobiol 1986; 44; 489–94PubMedGoogle Scholar
  61. 61.
    Gomer CJ, Ferrario A, Hayashi N, et al. Molecular cellular and tissue responses following photodynamic therapy. Lasers Surg Med 1988; 8: 450–63PubMedGoogle Scholar
  62. 62.
    Salet C, Moreno G. Photosensitization of mitochondria: molecular and cellular aspects. J Photochem Photobiol B 1990; 5: 133–50PubMedGoogle Scholar
  63. 63.
    Jori G, Spikes JD. Photochemistry of porphyrins. In: Smith KC, editor. Topics in photomedicine. New York: Plenum, 1984: 183–318Google Scholar
  64. 64.
    Evensen JF, Malik Z, Moan J. Ultrastructural changes in the nuclei of human carcinoma cells after photodynamic treatment with hematoporphyrin derivative and with tetrasodium-meso-tetra- (4-sulphonatophenyl) porphine. Lasers Med Sci 1988; 3: 195–206Google Scholar
  65. 65.
    Gomer CJ, Rucker N, Murphee AL. Differential cell photosensitivity following porphyrin photodynamic therapy. Cancer Res 1988; 48: 4539–42PubMedGoogle Scholar
  66. 66.
    Star WM, Marijnissen JPA, Van den Berg-Blok AE, et al. Destruction of rat mammary tumour and normal tissue microcirculation by hematoporphyrin derivative photoradiation observed in vivo in sandwich observation chambers. Cancer Res 1986; 46: 2532–40PubMedGoogle Scholar
  67. 67.
    Henderson BW, Waldow SM, Mang TS, et al. Tumor destruction and kinetics of tumor cell death in two experimental mouse tumors following photodynamic therapy. Cancer Res 1985; 45: 572–6PubMedGoogle Scholar
  68. 68.
    Selman SH, Kreimer-Birnbaum M, Klaunig JE, et al. Blood flow in transplantable bladder tumors treated with hematoporphyrin derivative and light. Cancer Res 1984; 44: 1924–7PubMedGoogle Scholar
  69. 69.
    Nelson JS, Liaw LH, Berns MW. Tumor destruction in photodynamic therapy. Photochem Photobiol 1987; 46: 829–35PubMedGoogle Scholar
  70. 70.
    Wilson BC, Patterson MS. The physics of photodynamic therapy. Phys Med Biol 1986; 31: 327–60PubMedGoogle Scholar
  71. 71.
    Marijnissen JPA, Star WM, Versteeg AAC, et al. Pilot study on the interstitial HPD-PDT in rats bearing solid mammary carcinoma or rhabdomyosarcoma. In: Jori G, Perria C, editors. Photodynamic therapy of tumours and other diseases. Padova: Liberia Progetto, 1985: 387–90Google Scholar
  72. 72.
    Muller PJ, Wilson BC. Photodynamic therapy of malignant primary brain tumors: clinical effects, post-operative ICP, and light penetration of the brain. Photochem Photobiol 1987; 46: 929–35PubMedGoogle Scholar
  73. 73.
    Arnfield M, Gonzalez S, Lea P, et al. Cylindrical irradiation fibre tip for photodynamic therapy. Lasers Surg Med 1986; 6: 150–4PubMedGoogle Scholar
  74. 74.
    Marijnissen JPA, Versteeg JAC, Star WM, et al. Tumor and normal tissue response to interstitial photodynamic therapy of the rat R-l rhabdomyosarcoma. Int J Radiat Oncol Biol Phys 1992; 22: 963–72PubMedGoogle Scholar
  75. 75.
    Star WM, Wilson BC, Patterson MS. Light delivery and optical dosimetry in photodynamic therapy of solid tumors. In: Henderson BW, Dougherty TJ, editors. Photodynamic therapy: basic principles and clinical applications. New York: Marcel Dekker, 1992: 335–67Google Scholar
  76. 76.
    Patterson MS, Wilson BC, Wyman DG. The propagation of optical radiation in tissue, I: models of transport and their application. Lasers Med Sci 1991; 6: 155–68Google Scholar
  77. 77.
    Patterson MS, Wilson BC, Wyman DG. The propagation of optical radiation in tissue, II: optical properties of tissues and resulting fluence distributions. Lasers Med Sci 1991; 6: 379–90Google Scholar
  78. 78.
    Marijnissen JPA, Star WM. Quantitative light dosimetry in vitro and in vivo. Lasers Med Sci 1987; 2: 235–41Google Scholar
  79. 79.
    Van Hillegersberg R, Pickering JW, Aalders M, et al. Optical properties for rat liver and tumour at 633 nm and 1064 nm: Photofrin® enhances scattering. Lasers Surg Med 1993; 13: 31–9PubMedGoogle Scholar
  80. 80.
    Marijnissen JPA, Jansen H, Star WM. Treatment system from whole bladder wall photodynamic therapy with in vivo monitoring and control of light dose rate and dose. J Urol 1989; 142: 1351–5Google Scholar
  81. 81.
    D’Hallewin MA, Baert L, Marijnissen JPA, et al. Whole bladder wall photodynamic therapy with in situ light dosimetry for carcinoma in situ of the bladder. J Urol 1992; 148: 1152–5PubMedGoogle Scholar
  82. 82.
    Arnfield MR, Tulip T, Chetner M, et al. Optical dosimetry for interstitial photodynamic therapy. Med Phys 1989; 16: 602–8PubMedGoogle Scholar
  83. 83.
    Van Hillegersberg R, Marijnissen JPA, Kort WJ, et al. Interstitial photodynamic therapy in a rat liver metastases model. Br J Cancer 1992; 66: 1005–14PubMedGoogle Scholar
  84. 84.
    Kreimer-Birnbaum M. Modified porphyrins, chlorins, phtalocyanines and purpurins: second-generation photosensitizers for photodynamic therapy. Semin Hematol 1989; 26: 157–73PubMedGoogle Scholar
  85. 85.
    Gomer CJ, Rucker N, Ferrario A, et al. Properties and applications of photodynamic therapy. Radiat Res 1989; 120: 1–18PubMedGoogle Scholar
  86. 86.
    Cannon JB. Pharmaceutics and drug delivery aspects of heme and porphyrin therapy. J Pharm Sci 1993; 82: 435–46PubMedGoogle Scholar
  87. 87.
    Kongshaug M, Moan J, Brown SB. The distribution of porphyrins with different tumour localizing ability among human plasma proteins. Br J Cancer 1989; 59: 184–8PubMedGoogle Scholar
  88. 88.
    Rosenthal I. Phtalocyanines as photodynamic sensitizers. Photochem Photobiol 1991; 53: 859–70PubMedGoogle Scholar
  89. 89.
    Ben-Hur E, Rosenthal I. The phtalocyanines: a new class of mammalian cell photosensitizers with a potential for cancer phototherapy. Int J Radiat Biol 1985; 47: 145–7Google Scholar
  90. 90.
    Brasseur N, Hasrat A, Langlois R, et al. Biological activities of phthalocyanines: photodynamic therapy of EMT-6 mammary tumors in mice with sulfonated phtalocyanines. Photochem Photobiol 1987; 45: 581–6PubMedGoogle Scholar
  91. 91.
    Roberts WG, Klein MK, Loomis M, et al. Photodynamic therapy of spontaneous cancers in felines, canines and snakes with chloro-aluminum sulfonated phtalocyanine. J Natl Cancer Inst 1991; 83: 18–23PubMedGoogle Scholar
  92. 92.
    Nelson JS, Roberts WG, Berns MW. In vivo studies on the utilization of mono-L-aspartyl chlorin (NPe6) for photodynamic therapy. Cancer Res 1987; 47: 4681–5PubMedGoogle Scholar
  93. 93.
    Roberts WG, Shiau FY, Nelson JS, et al. In vitro characterization of monoaspartyl chlorin e6 and diaspartyl chlorin e6 for photodynamic therapy. J Natl Cancer Inst 1988; 80: 330–6PubMedGoogle Scholar
  94. 94.
    Pandey RK, Bellnier DA, Smith KM, et al. Chlorin and porphyrin photosensitizers in photodynamic therapy. Photochem Photobiol 1991; 53: 65–72PubMedGoogle Scholar
  95. 95.
    Ris HB, Altermatt HJ, Inderbitzi R, et al. Photodynamic therapy with chlorins for diffuse malignant mesothelioma: initial clinical results. Br J Cancer 1991; 64: 1116–20PubMedGoogle Scholar
  96. 96.
    Morgan AR, Garbo GM, Kreimer-Birnbaum M, et al. Morphological study of the combined effect of purpurin derivatives and light on transplantable rat bladder tumors. Cancer Res 1987; 47: 496–8PubMedGoogle Scholar
  97. 97.
    Selman SH, Garbo GM, Keck RW, et al. A dose response analysis of purpurin derivatives used as photosensitizers for the photodynamic treatment of transplantable FANFT-induced urothelial tumors. J Urol 1987; 137: 1255–7PubMedGoogle Scholar
  98. 98.
    Beems EM, Dubbelman TMAR, Lugtenburg J, et al. Photosensitizing properties of bacteriochlorophillin a and bacteriochlorin a, two derivatives of bacteriochlorophyll a. Photochem Photobiol 1987; 46: 639–43PubMedGoogle Scholar
  99. 99.
    Schuitmaker JJ, Van Best JA, Van Delft L, et al. Bacteriochlorin a, a new photosensitizer in photodynamic therapy: in vivo results. Invest Opthalmol Vis Sci 1990; 31: 1444–50Google Scholar
  100. 100.
    Morgan AR, Rampersaud A, Keck RW, et al. Verdins: new photosensitizers for photodynamic therapy. Photochem Photobiol 1987b; 46: 441–4PubMedGoogle Scholar
  101. 101.
    Hayden RE, McLear PW, Morgan AR, et al. Verdins in photodynamic therapy of squamous cell carcinoma. Am J Otolaryngol 1990; 11: 125–30PubMedGoogle Scholar
  102. 102.
    Pangka VS, Morgan AR, Dophin D. Diels-Alder reactions of protoporphyrin IX dimethyl ester with electron-deficient alkynes. J Org Chem 1986; 51: 1094–100Google Scholar
  103. 103.
    Richter AM, Kelly B, Chow J, et al. Preliminary studies on a more effective photoxic agent than hematoporphyrin. J Natl Cancer Inst 1987; 79: 1327–32PubMedGoogle Scholar
  104. 104.
    Rubino GF, Rassetti L. Porphyrin metabolism in human neoplastic tissues. Panminerva Med 1966; 8: 290–2PubMedGoogle Scholar
  105. 105.
    Schoenfeld N, Epstein O, Lahav M, et al. The heme biosyn-thetic pathway in lymphocytes of patients with malignant lymphoproliferative disorders. Cancer Lett 1988; 43: 43–8PubMedGoogle Scholar
  106. 106.
    Leibovici L, Schoenfeld N, Yehoshua HA, et al. Activity of porphobilinogen deaminase in peripheral blood mononuclear cells of patients with metastatic cancer. Cancer 1988; 62: 2297–300PubMedGoogle Scholar
  107. 107.
    El-Sharabasy MMH, El-Waseef AM, Hafez MM, et al. Porphyrin metabolism in some malignant diseases. Br J Cancer 1992; 65: 409–12PubMedGoogle Scholar
  108. 108.
    Van Hillegersberg R, Van den berg JWO, Kort WJ, et al. Selective accumulation of endogenously produced porphyrins in a liver metastases model in rats. Gastroenterology 1992; 103: 647–51PubMedGoogle Scholar
  109. 109.
    Pottier R, Chow YFA, LaPlate JP, et al. Non-invasive technique for obtaining fluorescene excitation and emission spectra in vivo. Photochem Photobiol 1986; 44: 679–87PubMedGoogle Scholar
  110. 110.
    Dailey HA, Smith A. Differential interaction of porphyrins used in photoradiation therapy with ferrochelatase. Biochem J 1984; 223: 441–5PubMedGoogle Scholar
  111. 111.
    Smith A. Mechanisms of toxicity of photoactivated artificial porphyrins. Role of porphyrin-protein interactions. Ann NY Acad Sci 1987; 514: 309–22PubMedGoogle Scholar
  112. 112.
    Rimington C, Riley PA. The biochemical approach to cancer therapy: a short essay. Int J Biochem 1993; 25: 1385–93PubMedGoogle Scholar
  113. 113.
    Sandberg S, Romslo I. Phototoxicity of protoporphyrin as related to its subcellular localization in mice livers after short-term feeding with griseofulvin. Biochem J 1981; 198: 67–74PubMedGoogle Scholar
  114. 114.
    Rebeiz N, Rebeiz CC, Arkins S, et al. Photodestruction in tumor cells by induction of endogenous accumulation of pro-tporphyrin IX. Enhancement by 1,10-phenanthroline. Photochem Photobiol 1992; 55: 431–5PubMedGoogle Scholar
  115. 115.
    Ortel B, Tanew A, Honigsmann H. Lethal photosensitization by endogenous porphyrins of PAM cells: modification by desferrioxamine. J Photochem Photobiol B 1993; 17: 273–8PubMedGoogle Scholar
  116. 116.
    Grant WE, Hopper C, MAcRobert AJ, et al. Photodynamic therapy of oral cancer: photosensitization with systemic aminolevulinic acid. Lancet 1993; 342: 147–8PubMedGoogle Scholar
  117. 117.
    Loh CS, MacRobert AJ, Bedwell J, et al. Oral versus intravenous administration of 5-aminolevulinic acid for photodynamic therapy. Br J Cancer 1993; 68: 41–51PubMedGoogle Scholar
  118. 118.
    Grossner L, Hahn EG, Ell C. Oral administration of 5-aminolevulinic acid for photodynamic therapy in patients with gastrointestinal carcinomas: preliminary results. Gastroenterology 1994; 106: A387Google Scholar
  119. 119.
    Loh CS, Bedwell J, MacRobert AJ, et al. Photodynamic therapy of the normal rat stomach: a comparitive study betweeen disulfonated aluminium phthlocyanine and 5-aminolevulinic acid. Br J Cancer 1992; 66: 452–462PubMedGoogle Scholar
  120. 120.
    Loh CS, Vernon D, MacRobert AJ, et al. Endogenous porphyrin distribution induced by 5-aminolevulinic acid in the gastrointestinal tract. J Photochem Photobiol B 1993; 20: 47–54PubMedGoogle Scholar
  121. 121.
    Kennedy JC, Pottier RH, Pross DC. Photodynamic therapy with endogenous protoporphyrin IX. Basic principles and present clinical experience. J Photochem Photobiol B 1990; 6: 143–8PubMedGoogle Scholar
  122. 122.
    Szeimies RM, Sassy T, Landthaler M. Penetration of topical applied delta-aminolevulinic acid for photodynamic therapy of basal cell carcinoma. Photochem Photobiol 1994; 59: 73–6PubMedGoogle Scholar
  123. 123.
    Cairduff F, Stringer MR, Hudson EJ, et al. Superficial photodynamic therapy with topical 5-aminolevulinic acid for superficial primary and secondary skin cancer. Br J Cancer 1994; 69: 605–8Google Scholar
  124. 124.
    Wolf P, Rieger E, Kerl H. Topical photodynamic therapy with endogenous porphyrins after application of 5-aminolevulinic acid. J Am Acad Dermatol 1993; 28: 17–21PubMedGoogle Scholar
  125. 125.
    Kennedy JC, Pottier RH. Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy. J Photochem Photobiol B 1992; 275–92Google Scholar
  126. 126.
    Joseph R, Gofstein G, Jacques S. Photobleaching of 5-aminolevulinic acid induced protoporphyrin IX. Lasers Surg Med 1993; Suppl 5: 46Google Scholar
  127. 127.
    Konig K, Schneckenburger H, Ruck A, et al. In vivo photoproduct formation during PDT with ALA-induced endogenous porphyrins. J Photochem Photobiol B 1993; 18: 287–90PubMedGoogle Scholar
  128. 128.
    Bedwell J, MacRobert AJ, Phillips D, et al. Fluorescence distribution and photodynamic effect of ALA-induced PPIX in the DMH rat colonic tumour model. BrJ Cancer 1992; 65: 818–24Google Scholar
  129. 129.
    Roberts WG, Smith KM, McCullogh, et al. Skin photosensitivity and photodestruction of several potential photodynamic sensitizers. Photochem Photobiol 1989; 49: 431–8PubMedGoogle Scholar
  130. 130.
    Tralau CJ, Young AR, Walker NPJ, et al. Mouse skin photosen-sitivity with dihematoporphyrin ether (DHE) and aluminum sulphonated phtalocyanine (AISPc): a comparative study. Photochem Photobiol 1989; 49: 305–12PubMedGoogle Scholar
  131. 131.
    Richter AM, Ashok KJ, Obochi M, et al. Activation of benzoporphyrin derivative in the circulation of mice without skin photosenitivity. Photochem Photobiol 1994; 59: 350–5PubMedGoogle Scholar
  132. 132.
    Gibson SL, Vandermeid KR, Murant RS, et al. Effects of various photoradiation regimens on the antitumor efficacy of photodynamic therapy for R3230 AC mammary carcinomas. Cancer Res 1990; 50: 7236–41PubMedGoogle Scholar
  133. 133.
    Ferrario A, Rucker N, Ryter SW, et al. Direct comparison of in-vitro and in-vivo photofrin-II mediated photosensitization using a pulsed KTP pumped dye laser and continuous wave argon ion pumped dye laser. Lasers Surg Med 1991; 11: 404–10PubMedGoogle Scholar
  134. 134.
    Phillip MJ, McMahon JD, O’Hara MD, et al. Effects of hematoporphyrin (HpD) and a chemiluminescence system on the growth of transplanted tumors in C3H/HeJ mice. Prog Clin Biol Res 1984; 170: 563–9PubMedGoogle Scholar
  135. 135.
    Osersoff AR, Ara G, Ohuoha D, et al. Strategies for selective cancer photochemotherapy: antibody-targeted and selective carcinoma cell photolysis. Photochem Photobiol 1987; 46: 83–96Google Scholar
  136. 136.
    Rakestraw SL, Tompkins RG, Yarmush ML. Antibody-targeted photolysis: in vitro studies with Sn (IV) chlorin e6 covalently bound to monoclonal antibodies using a modified dextran carrier. Proc Natl Acad Sci USA 1990; 87: 4217–21PubMedGoogle Scholar
  137. 137.
    Yarmush ML, Thorpe WP, Strong L, et al. Antibody targeted photolysis. Crit Rev Ther Drug Carrier Syst 1993; 10: 197–252PubMedGoogle Scholar
  138. 138.
    Keene JP, Kessel D, Land EJ, et al. Direct detection of singlet oxygen sensitized by hematoporphyrin and related compounds. Photochem Photobiol 1986; 43: 117–20PubMedGoogle Scholar
  139. 139.
    Tromberg BJ, Orenstein A, Kimel S, et al. In vivo tumor oxygen tension measurements for the evaluation of the efficiency of photodynamic therapy. Photochem Photobiol 1990; 52: 375–85PubMedGoogle Scholar
  140. 140.
    Dodd NJF, Moore JV, Poppit DG, et al. In vivo magnetic resonance imaging of the effects of photodynamic therapy. Br J Cancer 1989; 60: 164–7PubMedGoogle Scholar
  141. 141.
    Moore JV, Dodd NJ, Wood B. Proton nuclear magnetic resonance imaging as a predictor of the outcome of photodynamic therapy of tumours. Br J Radiol 1989; 62: 869–70PubMedGoogle Scholar
  142. 142.
    Gibson SL, Ceckler TL, Bryant TG, et al. Effects of laser photodynamic therapy on tumor phosphate levels and pH assessed by 31P-NMR spectroscopy. Cancer Biochem Biophys 1989; 10: 319–28PubMedGoogle Scholar
  143. 143.
    Mattiello J, Evelhoch JL, Brown E, et al. Effect of photodynamic therapy on RIF-1 tumor metabolism and blood flow examined by 31P and 2H NMR spectroscopy. NMR Biomed 1990; 3: 64–70PubMedGoogle Scholar
  144. 144.
    Moore RB, Chapman JD, Morkrzanowski AD, et al. Non-invasive monitoring of photodynamic therapy with 99technetium HMPAO scintigraphy. Br J Cancer 1992; 65: 491–7PubMedGoogle Scholar
  145. 145.
    Waldow SM, Dougherty TJ. Interaction of hyperthermia and photoradiation therapy. Radiat Res 1984; 97: 380–5PubMedGoogle Scholar
  146. 146.
    Matsumoto N, Saito H, Miyoshi N, et al. Combination effect of hyperthermia and photodynamic therapy on colon carcinoma. Arch Otolaryngol Head Neck Surg 1990; 116: 824–29PubMedGoogle Scholar
  147. 147.
    Glassberg E, Lewandowski L, Halcin C, et al. Hyperthermia potentiates the effects of aluminum phthalocyanine ter-tasulfonate-mediated photodynamic toxicity in human malignant and normal cell lines. Lasers Surg Med 1991; 11: 432–9PubMedGoogle Scholar
  148. 148.
    Waldow SM, Henderson BW, Dougherty TJ. Potentiation of photodynamic therapy by heat: effect of sequence and time interval between treatments in vivo. Lasers Surg Med 1985; 5: 83–94PubMedGoogle Scholar
  149. 149.
    Waldow SM, Henderson BW, Dougherty TJ. Hyperthermic potentiation of photodynamic therapy employing Photofrin® I and II: comparison of results using three animal tumor models. Lasers Surg Med 1987; 7: 12–22PubMedGoogle Scholar
  150. 150.
    Mang TS. Combinations studies of hyperthermia induced by neodymium: yttrium-aluminum-garnet (Nd:YAG) laser as an adjuvant to photodynamic therapy. Lasers Surg Med 1990; 10: 173–8PubMedGoogle Scholar
  151. 151.
    Gonzalez S, Arnfield MR, Meeker BE, et al. Treatment of Dunning R3327-AT rat prostate tumors with photodynamic therapy in combination with misonidazole. Cancer Res 1986; 46: 2858–62PubMedGoogle Scholar
  152. 152.
    Pottier R, Kennedy JC. The possible role of ionic species in selective biodistribution of photochemotherapeutic agents toward neoplastic tissue. J Photochem Photobiol 1990; 8: 1–16Google Scholar
  153. 153.
    Thomas JP, Girotti AW. Glucose administration augments in vivo uptake and phototoxicity of the tumor-localizing fraction of hematoporphyrin derivative. Photochem Photobiol 1989; 49: 241–7PubMedGoogle Scholar
  154. 154.
    Nelson JS, Kimel S, Brown L, et al. Glucose administration combined with photodynamic therapy of cancer improves therapeutic efficacy. Lasers Surg Med 1992; 12: 153–8PubMedGoogle Scholar
  155. 155.
    Cowled PA, Forbes IJ. Modification by vasoactive drugs of tumor destruction by photodynamic therapy with hematoporphyrin derivative. Br J Cancer 1989; 59: 904–9PubMedGoogle Scholar
  156. 156.
    Pass HI. Photodynamic therapy in oncology: mechanisms and clinical use. J Natl Cancer Inst 1993; 85: 443–56PubMedGoogle Scholar
  157. 157.
    Dougherty TJ. Photodynamic therapy. Photochem Photobiol 1993; 58: 895–900PubMedGoogle Scholar
  158. 158.
    Puolakkainen P, Schröder T. Photodynamic therapy of gastrointestinal tumors: a review. Dig Dis 1992; 10: 53–60PubMedGoogle Scholar
  159. 159.
    Holland R, Veling SHJ, Mravunac M, et al. Histologic multi-focality of Tis T1–2 breast carcinomas. Cancer 1985; 56: 979–90PubMedGoogle Scholar
  160. 160.
    Buyse M, Zeleniuch-Jacquotte A, Chalmers TC. Adjuvant therapy of colorectal cancer: why we still don’t know. JAMA 1988; 259: 3571–611PubMedGoogle Scholar
  161. 161.
    Frazier TG, Wong RWY, Rose D. Implications of accurate pathological margins in the treatment of primary breast cancer. Arch Surg 1989; 124: 37–8PubMedGoogle Scholar
  162. 162.
    Herrera-Ornelas L, Petrilli NJ, Mittelman A. Photodynamic therapy in patients with colorectal cancer. Cancer 1986; 57: 677–84PubMedGoogle Scholar
  163. 163.
    Nambisan RN, Karakousis CP, Holyoke ED, et al. Intraoperative photodynamic therapy for retroperitoneal sarcomas. Cancer 1988; 61: 1248–52PubMedGoogle Scholar
  164. 164.
    Delaney TF, Sindelar WF, Tochner Z, et al. Phase I study of debulking surgery and photodynamic therapy for disseminated intraperitoneal tumors. Int J Radiat Oncol Biol Phys 1993; 25: 445–57PubMedGoogle Scholar
  165. 165.
    Abulafi AM, Alardice JT, Williams NS. Adjunctive intraoperative photodynamic therapy for colorectal cancer. Lasers Surg Med 1992; Suppl 4: 49Google Scholar
  166. 166.
    Abulafi AM, Alardice JT, Williams NS. A Phase III study on the effect of adjunctive intraoperative photodynamic therapy in colorectal cancer: an interim report. Lasers Surg Med 1993; Suppl. 5: 45Google Scholar
  167. 167.
    Lantz JM, Meyer C, Saussine C, et al. Experimental photodynamic therapy with a copper metal vapor laser in colorectal cancer. Int J Cancer 1992; 52: 491–8PubMedGoogle Scholar
  168. 168.
    Davis RK, Smith LF, Thurgood RF, et al. Intraoperative phototherapy (PDT) and surgical resection in a mouse neu-roblastoma model. Lasers Surg Med 1990; 10: 275–9PubMedGoogle Scholar
  169. 169.
    Van Hillegersberg R, Hekking-Weijma JM, Wilson JHP, et al. Adjuvant intraoperative photodynamic therapy diminishes the rate of local recurrence in a rat mammary tumour model. Submitted.Google Scholar
  170. 170.
    Evrard S, Aprahamian M, Marescaux J. Intra-operative photodynamic therapy: from theory to feasibility. Br J Surg 1993; 80: 298–303PubMedGoogle Scholar

Copyright information

© Adis International Limited 1994

Authors and Affiliations

  • Richard van Hillegersberg
    • 1
  • Will J. Kort
    • 1
  • J. H. Paul Wilson
    • 1
  1. 1.Erasmus University, Medical FacultyRotterdamThe Netherlands

Personalised recommendations