Skip to main content
SpringerLink
Log in

Current Status of Photodynamic Therapy in Oncology

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Summary

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Raab O. Über die Wirkung fluoreszierender Stoffe auf Infusoria. Z Biol 1900; 39: 524–6

    CAS  Google Scholar 

  2. Tappeiner HV, Jesionek A. Therapeutische Versuche mit fluoreszierenden Stoffe. Muench Med Wochenschr 1903; 47: 2042–4

    Google Scholar 

  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: 476–503

    Google Scholar 

  4. Auler H, Banzer G. Untersuchungen über die Rolle der Porphyrine bei geschwulstkranke Menschen und Tieren. Z Krebsforsch. 1942; 53: 65–8

    CAS  Google Scholar 

  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: 640–1

    CAS  Google Scholar 

  6. Schwartz S, Absolon K, Vermund H. Some relationships of porphyrins, x-rays, and tumors. Univ Minnesota Med Bull 1955; 7: 7–13

    Google Scholar 

  7. Lipson RL, Blades EJ, Olsen AM. The use of hematoporphyrin in tumour destruction. J Natl Cancer Inst 1961; 26: 1–11

    PubMed  CAS  Google Scholar 

  8. Diamond I, Granelli SG, McDonagh AF, et al. Photodynamic therapy of malignant tumors. Lancet 1972; 2: 1175–7

    PubMed  CAS  Google Scholar 

  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: 115–21

    PubMed  CAS  Google Scholar 

  10. Kelly JF, Snell ME. Hematoporphyrin derivative: a possible aid in the diagnosis and therapy of carcinoma of the bladder. J Urol 1976; 155: 150–1

    Google Scholar 

  11. Dougherty TJ. Photodynamic therapy (PDT) of malignant tumors. Crit Rev Oncol Hematol 1984; 2: 83–116

    PubMed  CAS  Google Scholar 

  12. Dougherty TJ, Potter WR, Weishaupt KR. The structure of the active component of hematoporphyrin derivative. Prog Clin Biol Res 1984; 170: 301–14

    PubMed  CAS  Google Scholar 

  13. Dougherty TJ, Marcus SL. Photodynamic therapy. Eur J Cancer 1992; 28A: 1734–42

    PubMed  CAS  Google Scholar 

  14. Dougherty TJ. Studies on the structure of porphyrins contained in Photofrin® II. Photochem Photobiol 1987a; 46: 569–73

    PubMed  CAS  Google Scholar 

  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: 4642–5

    PubMed  CAS  Google Scholar 

  16. Dougherty TJ. Photodynamic therapy: new approaches. Semin Surg Oncol 1989; 5: 6–16

    PubMed  CAS  Google Scholar 

  17. Dougherty TJ. Photosensitization of malignant tumors. Semin Surg Oncol 1986; 2: 24–37

    PubMed  CAS  Google Scholar 

  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: 925–8

    PubMed  CAS  Google Scholar 

  19. Dougherty TJ, Cooper MT, Mang TS. Cutaneous phototoxic occurrences in patients receiving photofrin. Lasers Surg Med 1990; 10: 485–8

    PubMed  CAS  Google Scholar 

  20. Bellnier DA, Ho YK, Pandey RK, et al. Distribution and elimination of Photofrin® II in mice. Photochem Photobiol 1989; 50: 221–8

    PubMed  CAS  Google Scholar 

  21. Jori G. Photodynamic therapy of solid tumors. Radiat Phys Chem 1987; 30: 375–80

    CAS  Google Scholar 

  22. Dougherty TJ. Photosensitizers: therapy and detection of malignant tumors. Photochem Photobiol 1987; 45: 879–89

    PubMed  CAS  Google Scholar 

  23. Jori G, Reddi E. The role of lipoproteins in the delivery of tumour-targeting photosensitizers. Int J Biochem 1993; 25: 1369–75

    PubMed  CAS  Google Scholar 

  24. Jori G. In vivo transport and pharmacokinetic behavior of tumour photosensitizers. Ciba Found Symp 1989; 146: 78–94

    PubMed  CAS  Google Scholar 

  25. Korbelik M, Hung J. Cellular delivery and retention of Photofrin®: II. The effects of interaction with human plasma proteins. Photochem Photobiol 1991; 53: 501–10

    PubMed  CAS  Google Scholar 

  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: 291–7

    PubMed  CAS  Google Scholar 

  27. Kessel D. Porphyrin lipoprotein association as a factor in porphyrin localization. Cancer Lett 1986; 33: 183–8

    PubMed  CAS  Google Scholar 

  28. Gomer CJ, Dougherty TJ. Determination of (3H)- and (14C) hematoporphyrin derivative distribution in malignant and normal tissue. Cancer Res 1979; 39: 146–51

    PubMed  CAS  Google Scholar 

  29. Bugelski PJ, Porter CW, Dougherty TJ. Autoradiographic distribution of hematoporphyrin derivative in normal and tumour tissue of the mouse. Cancer Res 1981; 41: 4606–12

    PubMed  CAS  Google Scholar 

  30. Wilson BC, Van Lier. Radiolabelled photosensitizers for tumor imaging and photodynamic therapy. J Photochem Photobiol B 1989; 3: 459–63

    PubMed  CAS  Google Scholar 

  31. Spikes JD, Jori G. Photodynamic therapy of tumours and other diseases. Lasers Med Sci 1987; 2: 3–15

    Google Scholar 

  32. Kessel D, Woodburn K. Biodistribution of photosensitizing agents. Int J Biochem 1993; 25: 1377–83

    PubMed  CAS  Google Scholar 

  33. Wilson JHP, Van Hillegersberg R, Van den Berg JWO, et al. Photodynamic therapy for gastrointestinal tumors. Scand J Gastroenterol 1991; 188 Suppl. 26: 20–5

    CAS  Google Scholar 

  34. Wilson BC. Photodynamic therapy: light delivery and dosage for second-generation photosensitizers. Ciba Found Symp 1989; 146: 60–77

    PubMed  CAS  Google Scholar 

  35. Bonnet R, Berenbaum M. Porhpyrins as photosensitizers. Ciba Found Symp 1989; 146: 40–59

    Google Scholar 

  36. Van Gemert MJC, Berenbaum MC, Gijsberts GHM. Wavelength and light-dose dependence in tumour phototherapy with hematoporphyrin derivative. Br J Cancer1985; 52: 43–9

    PubMed  Google Scholar 

  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: 153–62

    Google Scholar 

  38. Gomer CJ, Doiron DR, Rucker N, et al. Action spectrum (620-640 nm) for hematoporphyrin derivative induced cell killing. Photochem Photobiol1984; 39: 365–8

    PubMed  CAS  Google Scholar 

  39. Star WM, Versteeg J, Van Putten W, et al. Wavelength dependence of hematoporphyrin derivative photodynamic treatment on rat ears. Photochem Photobiol1990; 52: 547–54

    PubMed  CAS  Google Scholar 

  40. Weishaupt KR, Gomer CJ, Dougherty TJ. Identification of singlet oxygen as the cytotoxic agent in photoactivation of a murine tumour. Cancer Res1976; 36: 2326–9

    PubMed  CAS  Google Scholar 

  41. Gomer CJ, Razum NJ. Acute skin response in albino mice following porphyrin photosensitization under oxic and anoxic conditions. Photochem Photobiol1984; 40: 435–9

    PubMed  CAS  Google Scholar 

  42. Mitchell JB, McPhearson S, DeGraff W, et al. Oxygen dependence of hematoporphyrin derivative induced photoinactivation of Chinese Hamster cells. Cancer Res1985; 45: 2008–11

    PubMed  CAS  Google Scholar 

  43. Moan J, Sommer S. Oxygen dependence of the photosensitizing effect of hematoporphyrin derivative in NHIK-3025 cells. Cancer Res1985; 45: 1608–10

    PubMed  CAS  Google Scholar 

  44. Henderson BW, Fingar VH. Oxygen limitation of direct tumour cell kill during photodynamic treatment of a murine tumour model. Photochem Photobiol1989; 49: 299–304

    PubMed  CAS  Google Scholar 

  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: 73–9

    PubMed  CAS  Google Scholar 

  46. Valenzo DP. Photomodification of biological membranes with emphasis on singlet oxygen mechanisms. Photochem Photobiol1987; 46: 147–60

    Google Scholar 

  47. Foote CS. Definition of type I and type II photosensitized oxidation. Photochem Photobiol1991; 54: 659

    PubMed  CAS  Google Scholar 

  48. Gomer CJ. Photodynamic therapy in the treatment of malignancies. Semin Hematol1989; 26: 27–34

    PubMed  CAS  Google Scholar 

  49. Buettner GR, Need MJ. Hydrogen peroxide and hydroxyl free radical production by hematoporphyrin derivative, ascorbate and light. Cancer Lett 1985; 25: 297–304

    PubMed  CAS  Google Scholar 

  50. Van Steveninck J, Tijssen K, Boegheim JP, et al. Photodynamic generation of hydroxyl radicals by hematoporphyrin derivative and light. Photochem Photobiol 1986; 44: 711–6

    PubMed  Google Scholar 

  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: 1137–43

    PubMed  CAS  Google Scholar 

  52. Mang TS, Dougherty TJ, Potter WR, et al. Photobleaching of porphyrins used in photodynamic therapy and implications for therapy. Photochem Photobiol 1987; 45: 501–6

    PubMed  CAS  Google Scholar 

  53. Potter WR, Mang TS, Dougherty TJ. The theory of photodynamic dosimetry: consequences of photodestruction of sensitizers. Photochem Photobiol 1987; 46: 97–101

    PubMed  CAS  Google Scholar 

  54. Boyle DG, Potter WR. Photobleaching of photofrin II as a means of eliminating skin photosensitivity. Photochem Photobiol 1987; 46: 997–1001

    PubMed  CAS  Google Scholar 

  55. Zhou C. Mechanisms of tumor necrosis induced by photodynamic therapy. J Photochem Photobiol 1989; 3: 299–318

    CAS  Google Scholar 

  56. Moan J, Berg K, Kvam E, et al. Intracellular localization of photosensitizers. Ciba Found Symp 1989; 146: 95–111

    PubMed  CAS  Google Scholar 

  57. Jori G. Photosensitized processes in-vivo: proposed phototherapeutic applications. Photochem Photobiol 1990; 52: 439–43

    PubMed  CAS  Google Scholar 

  58. Girotti AW. Photodynamic lipid peroxidation in biological systems. Photochem Photobiol 1990; 51: 497–509

    PubMed  CAS  Google Scholar 

  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: 98–103

    PubMed  CAS  Google Scholar 

  60. Kessel D. Sites of photosensitization by derivates of hematoporphyrin. Photochem Photobiol 1986; 44; 489–94

    PubMed  CAS  Google Scholar 

  61. Gomer CJ, Ferrario A, Hayashi N, et al. Molecular cellular and tissue responses following photodynamic therapy. Lasers Surg Med 1988; 8: 450–63

    PubMed  CAS  Google Scholar 

  62. Salet C, Moreno G. Photosensitization of mitochondria: molecular and cellular aspects. J Photochem Photobiol B 1990; 5: 133–50

    PubMed  CAS  Google Scholar 

  63. Jori G, Spikes JD. Photochemistry of porphyrins. In: Smith KC, editor. Topics in photomedicine. New York: Plenum, 1984: 183–318

    Google Scholar 

  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: 195–206

    Google Scholar 

  65. Gomer CJ, Rucker N, Murphee AL. Differential cell photosensitivity following porphyrin photodynamic therapy. Cancer Res 1988; 48: 4539–42

    PubMed  CAS  Google Scholar 

  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: 2532–40

    PubMed  CAS  Google Scholar 

  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: 572–6

    PubMed  CAS  Google Scholar 

  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: 1924–7

    PubMed  CAS  Google Scholar 

  69. Nelson JS, Liaw LH, Berns MW. Tumor destruction in photodynamic therapy. Photochem Photobiol 1987; 46: 829–35

    PubMed  CAS  Google Scholar 

  70. Wilson BC, Patterson MS. The physics of photodynamic therapy. Phys Med Biol 1986; 31: 327–60

    PubMed  CAS  Google Scholar 

  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: 387–90

    Google Scholar 

  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: 929–35

    PubMed  CAS  Google Scholar 

  73. Arnfield M, Gonzalez S, Lea P, et al. Cylindrical irradiation fibre tip for photodynamic therapy. Lasers Surg Med 1986; 6: 150–4

    PubMed  CAS  Google Scholar 

  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: 963–72

    PubMed  CAS  Google Scholar 

  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: 335–67

    Google Scholar 

  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: 155–68

    Google Scholar 

  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: 379–90

    Google Scholar 

  78. Marijnissen JPA, Star WM. Quantitative light dosimetry in vitro and in vivo. Lasers Med Sci 1987; 2: 235–41

    Google Scholar 

  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: 31–9

    PubMed  Google Scholar 

  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: 1351–5

    Google Scholar 

  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: 1152–5

    PubMed  Google Scholar 

  82. Arnfield MR, Tulip T, Chetner M, et al. Optical dosimetry for interstitial photodynamic therapy. Med Phys 1989; 16: 602–8

    PubMed  CAS  Google Scholar 

  83. Van Hillegersberg R, Marijnissen JPA, Kort WJ, et al. Interstitial photodynamic therapy in a rat liver metastases model. Br J Cancer 1992; 66: 1005–14

    PubMed  Google Scholar 

  84. Kreimer-Birnbaum M. Modified porphyrins, chlorins, phtalocyanines and purpurins: second-generation photosensitizers for photodynamic therapy. Semin Hematol 1989; 26: 157–73

    PubMed  CAS  Google Scholar 

  85. Gomer CJ, Rucker N, Ferrario A, et al. Properties and applications of photodynamic therapy. Radiat Res 1989; 120: 1–18

    PubMed  CAS  Google Scholar 

  86. Cannon JB. Pharmaceutics and drug delivery aspects of heme and porphyrin therapy. J Pharm Sci 1993; 82: 435–46

    PubMed  CAS  Google Scholar 

  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: 184–8

    PubMed  CAS  Google Scholar 

  88. Rosenthal I. Phtalocyanines as photodynamic sensitizers. Photochem Photobiol 1991; 53: 859–70

    PubMed  CAS  Google Scholar 

  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: 145–7

    CAS  Google Scholar 

  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: 581–6

    PubMed  CAS  Google Scholar 

  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: 18–23

    PubMed  CAS  Google Scholar 

  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: 4681–5

    PubMed  CAS  Google Scholar 

  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: 330–6

    PubMed  CAS  Google Scholar 

  94. Pandey RK, Bellnier DA, Smith KM, et al. Chlorin and porphyrin photosensitizers in photodynamic therapy. Photochem Photobiol 1991; 53: 65–72

    PubMed  CAS  Google Scholar 

  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: 1116–20

    PubMed  CAS  Google Scholar 

  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: 496–8

    PubMed  CAS  Google Scholar 

  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: 1255–7

    PubMed  CAS  Google Scholar 

  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: 639–43

    PubMed  CAS  Google Scholar 

  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: 1444–50

    CAS  Google Scholar 

  100. Morgan AR, Rampersaud A, Keck RW, et al. Verdins: new photosensitizers for photodynamic therapy. Photochem Photobiol 1987b; 46: 441–4

    PubMed  CAS  Google Scholar 

  101. Hayden RE, McLear PW, Morgan AR, et al. Verdins in photodynamic therapy of squamous cell carcinoma. Am J Otolaryngol 1990; 11: 125–30

    PubMed  CAS  Google Scholar 

  102. Pangka VS, Morgan AR, Dophin D. Diels-Alder reactions of protoporphyrin IX dimethyl ester with electron-deficient alkynes. J Org Chem 1986; 51: 1094–100

    CAS  Google Scholar 

  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: 1327–32

    PubMed  CAS  Google Scholar 

  104. Rubino GF, Rassetti L. Porphyrin metabolism in human neoplastic tissues. Panminerva Med 1966; 8: 290–2

    PubMed  CAS  Google Scholar 

  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: 43–8

    PubMed  CAS  Google Scholar 

  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: 2297–300

    PubMed  CAS  Google Scholar 

  107. El-Sharabasy MMH, El-Waseef AM, Hafez MM, et al. Porphyrin metabolism in some malignant diseases. Br J Cancer 1992; 65: 409–12

    PubMed  CAS  Google Scholar 

  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: 647–51

    PubMed  Google Scholar 

  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: 679–87

    PubMed  CAS  Google Scholar 

  110. Dailey HA, Smith A. Differential interaction of porphyrins used in photoradiation therapy with ferrochelatase. Biochem J 1984; 223: 441–5

    PubMed  CAS  Google Scholar 

  111. Smith A. Mechanisms of toxicity of photoactivated artificial porphyrins. Role of porphyrin-protein interactions. Ann NY Acad Sci 1987; 514: 309–22

    PubMed  CAS  Google Scholar 

  112. Rimington C, Riley PA. The biochemical approach to cancer therapy: a short essay. Int J Biochem 1993; 25: 1385–93

    PubMed  CAS  Google Scholar 

  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: 67–74

    PubMed  CAS  Google Scholar 

  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: 431–5

    PubMed  CAS  Google Scholar 

  115. Ortel B, Tanew A, Honigsmann H. Lethal photosensitization by endogenous porphyrins of PAM cells: modification by desferrioxamine. J Photochem Photobiol B 1993; 17: 273–8

    PubMed  CAS  Google Scholar 

  116. Grant WE, Hopper C, MAcRobert AJ, et al. Photodynamic therapy of oral cancer: photosensitization with systemic aminolevulinic acid. Lancet 1993; 342: 147–8

    PubMed  CAS  Google Scholar 

  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: 41–51

    PubMed  CAS  Google Scholar 

  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: A387

    Google Scholar 

  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: 452–462

    PubMed  CAS  Google Scholar 

  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: 47–54

    PubMed  CAS  Google Scholar 

  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: 143–8

    PubMed  CAS  Google Scholar 

  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: 73–6

    PubMed  CAS  Google Scholar 

  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: 605–8

    Google Scholar 

  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: 17–21

    PubMed  CAS  Google Scholar 

  125. Kennedy JC, Pottier RH. Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy. J Photochem Photobiol B 1992; 275–92

  126. Joseph R, Gofstein G, Jacques S. Photobleaching of 5-aminolevulinic acid induced protoporphyrin IX. Lasers Surg Med 1993; Suppl 5: 46

    Google Scholar 

  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: 287–90

    PubMed  CAS  Google Scholar 

  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: 818–24

    CAS  Google Scholar 

  129. Roberts WG, Smith KM, McCullogh, et al. Skin photosensitivity and photodestruction of several potential photodynamic sensitizers. Photochem Photobiol 1989; 49: 431–8

    PubMed  CAS  Google Scholar 

  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: 305–12

    PubMed  CAS  Google Scholar 

  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: 350–5

    PubMed  CAS  Google Scholar 

  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: 7236–41

    PubMed  CAS  Google Scholar 

  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: 404–10

    PubMed  CAS  Google Scholar 

  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: 563–9

    PubMed  CAS  Google Scholar 

  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: 83–96

    Google Scholar 

  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: 4217–21

    PubMed  CAS  Google Scholar 

  137. Yarmush ML, Thorpe WP, Strong L, et al. Antibody targeted photolysis. Crit Rev Ther Drug Carrier Syst 1993; 10: 197–252

    PubMed  CAS  Google Scholar 

  138. Keene JP, Kessel D, Land EJ, et al. Direct detection of singlet oxygen sensitized by hematoporphyrin and related compounds. Photochem Photobiol 1986; 43: 117–20

    PubMed  CAS  Google Scholar 

  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: 375–85

    PubMed  CAS  Google Scholar 

  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: 164–7

    PubMed  CAS  Google Scholar 

  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: 869–70

    PubMed  CAS  Google Scholar 

  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: 319–28

    PubMed  CAS  Google Scholar 

  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: 64–70

    PubMed  CAS  Google Scholar 

  144. Moore RB, Chapman JD, Morkrzanowski AD, et al. Non-invasive monitoring of photodynamic therapy with 99technetium HMPAO scintigraphy. Br J Cancer 1992; 65: 491–7

    PubMed  CAS  Google Scholar 

  145. Waldow SM, Dougherty TJ. Interaction of hyperthermia and photoradiation therapy. Radiat Res 1984; 97: 380–5

    PubMed  CAS  Google Scholar 

  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: 824–29

    PubMed  CAS  Google Scholar 

  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: 432–9

    PubMed  CAS  Google Scholar 

  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: 83–94

    PubMed  CAS  Google Scholar 

  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: 12–22

    PubMed  CAS  Google Scholar 

  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: 173–8

    PubMed  CAS  Google Scholar 

  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: 2858–62

    PubMed  CAS  Google Scholar 

  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: 1–16

    CAS  Google Scholar 

  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: 241–7

    PubMed  CAS  Google Scholar 

  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: 153–8

    PubMed  CAS  Google Scholar 

  155. Cowled PA, Forbes IJ. Modification by vasoactive drugs of tumor destruction by photodynamic therapy with hematoporphyrin derivative. Br J Cancer 1989; 59: 904–9

    PubMed  CAS  Google Scholar 

  156. Pass HI. Photodynamic therapy in oncology: mechanisms and clinical use. J Natl Cancer Inst 1993; 85: 443–56

    PubMed  CAS  Google Scholar 

  157. Dougherty TJ. Photodynamic therapy. Photochem Photobiol 1993; 58: 895–900

    PubMed  CAS  Google Scholar 

  158. Puolakkainen P, Schröder T. Photodynamic therapy of gastrointestinal tumors: a review. Dig Dis 1992; 10: 53–60

    PubMed  CAS  Google Scholar 

  159. Holland R, Veling SHJ, Mravunac M, et al. Histologic multi-focality of Tis T1–2 breast carcinomas. Cancer 1985; 56: 979–90

    PubMed  CAS  Google Scholar 

  160. Buyse M, Zeleniuch-Jacquotte A, Chalmers TC. Adjuvant therapy of colorectal cancer: why we still don’t know. JAMA 1988; 259: 3571–611

    PubMed  CAS  Google Scholar 

  161. Frazier TG, Wong RWY, Rose D. Implications of accurate pathological margins in the treatment of primary breast cancer. Arch Surg 1989; 124: 37–8

    PubMed  CAS  Google Scholar 

  162. Herrera-Ornelas L, Petrilli NJ, Mittelman A. Photodynamic therapy in patients with colorectal cancer. Cancer 1986; 57: 677–84

    PubMed  CAS  Google Scholar 

  163. Nambisan RN, Karakousis CP, Holyoke ED, et al. Intraoperative photodynamic therapy for retroperitoneal sarcomas. Cancer 1988; 61: 1248–52

    PubMed  CAS  Google Scholar 

  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: 445–57

    PubMed  CAS  Google Scholar 

  165. Abulafi AM, Alardice JT, Williams NS. Adjunctive intraoperative photodynamic therapy for colorectal cancer. Lasers Surg Med 1992; Suppl 4: 49

    Google Scholar 

  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: 45

  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: 491–8

    PubMed  CAS  Google Scholar 

  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: 275–9

    PubMed  CAS  Google Scholar 

  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.

  170. Evrard S, Aprahamian M, Marescaux J. Intra-operative photodynamic therapy: from theory to feasibility. Br J Surg 1993; 80: 298–303

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Erasmus University, Medical Faculty, Rotterdam, The Netherlands

    Richard van Hillegersberg, Will J. Kort & J. H. Paul Wilson

Authors
  1. Richard van Hillegersberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Will J. Kort
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. H. Paul Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

van Hillegersberg, R., Kort, W.J. & Wilson, J.H.P. Current Status of Photodynamic Therapy in Oncology. Drugs 48, 510–527 (1994). https://doi.org/10.2165/00003495-199448040-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-199448040-00003

Keywords

Search

Navigation