Skip to main content
Log in

Photodynamic Therapy in the Treatment of Cancer

Current State of the Art

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

Abstract

Photodynamic therapy (PDT) is a treatment modality using a photosensitising drug and light to kill cells. The clinical use of PDT requires the presence of a photosensitising agent, oxygen and light of a specific wavelength which matches the absorption characteristics of the photosensitiser. When the photosensitiser is activated by the appropriate wavelength of light, it interacts with molecular oxygen to form a toxic, short-lived species known as singlet oxygen, which is thought to mediate cellular death. The appeal of PDT in oncology is that the photosensitiser tends to be retained in tumour tissues for a longer period of time as compared with normal tissues resulting in a large therapeutic index. This potential for minimal normal tissue toxicity has prompted an interest in studying PDT as a cancer treatment. Furthermore, the use of PDT is not precluded by prior radiotherapy, chemotherapy or surgery. The development of PDT has been hampered by the limitations of the older photosensitisers, namely limited depth of tissue penetration, and extended skin phototoxicity which limits the number of applications during a course of treatment. However, newer photosensitisers are being developed which allow greater depth of tissue penetration and have minimal skin phototoxicity allowing for multiple fractionated treatments. With such advancements, PDT has great potential to become an integral part of cancer treatment in the future.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Lipson RL, Baldes EJ, Olsen EM. The use of a derivative of hematoporphyrin in tumor detection. J Natl Cancer Inst 1961; 26: 1

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Miller DS. The use of the laser in gynecology. J S C Med Assoc 1983; 79: 627–30

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  5. Moan J, Berg K. The photodegredation of porphyrins in cells can be used to estimate the lifetime of singlet oxygen. Photochem Photobiol 1991; 53: 549–53

    Article  PubMed  CAS  Google Scholar 

  6. Moan J, Pettersen EO, Christensen T. The mechanism of photodynamic inactivation of human cells in vitro in the presence of haematoporphyrin. Br J Cancer 1979; 39: 398–407

    Article  PubMed  CAS  Google Scholar 

  7. Volden G, Christensen T, Moan J. Photodynamic membrane damage of hematoporphyrin derivative-treated NHIK 3025 cells in vitro. Photobiochem Photobiophys 1981; 3: 105–11

    CAS  Google Scholar 

  8. Gibson SL, Murant RS, Hilf R. Photosensitizing effects of hematoporphyrin derivative and photofrin II on the plasma membrane enzymes 5′-nucleotidase, Na+ K+-ATPase, and Mg2+-ATPase in R3230AC rat mammary adenocarcinomas. Cancer Res 1988; 48: 3360–6

    PubMed  CAS  Google Scholar 

  9. Russo A, DeGraff W, Kinsella TJ, et al. Potentiation of chemotherapy cytotoxicity following iododeoxyuridine incorporation in Chinese hamster cells. Int J Radiat Oncol Biol Phys 1986; 12: 1371–4

    Article  PubMed  CAS  Google Scholar 

  10. Gomer CJ, Rucker N, Banerjee A, et al. Comparison of mutagenicity and induction of sister chromatid exchange in Chinese hamster cells exposed to derivative, ionizing radiation, or ultraviolet radiation. Cancer Res 1983; 43: 2622–7

    PubMed  CAS  Google Scholar 

  11. Moan J, Waksvik H, Christensen T. DNA single-stranded breaks and sister chromatid exchanges induced by treatment with hematoporphyrin and light or by x-rays in human NHIK 3025 cells. Cancer Res 1980; 40: 2915–8

    PubMed  CAS  Google Scholar 

  12. Mitchell JB, Russo A, Kinsella TJ, et al. The use of non-hypoxic cell sensitizers in radiobiology and radiotherapy. Int J Radiat Oncol Biol Phys 1986; 12: 1513–8

    Article  PubMed  CAS  Google Scholar 

  13. Fingar VH, Siegel KA, Wieman TJ, et al. The effects of thromboxane inhibitors on the microvascular and tumor response to photodynamic therapy. Photochem Photobiol 1993; 58: 393–9

    Article  PubMed  CAS  Google Scholar 

  14. Fingar VH, Wieman TJ, Haydon PS. The effects of thrombocytopenia on vessel stasis and macromolecular leakage after photodynamic therapy using Photofrin. Photochem Photobiol 1997; 66: 513–7

    Article  PubMed  CAS  Google Scholar 

  15. Fingar VH, Wieman TJ, Karavolos PS, et al. The effects of photodynamic therapy using differently substituted zinc phthalocyanines on vessel constriction, vessel leakage and tumor response. Photochem Photobiol 1993; 58: 251–8

    Article  PubMed  CAS  Google Scholar 

  16. McMahon KS, Wieman TJ, Moore PH, et al. Effects of photodynamic therapy using mono-L-aspartyl chlorin e6 on vessel constriction, vessel leakage, and tumor response. Cancer Res 1994; 54: 5374–9

    PubMed  CAS  Google Scholar 

  17. Gilissen MJ, van de Merbel-de Wit LE, Star WM, et al. Effect of photodynamic therapy on the endothelium-dependent relaxation of isolated rat aortas. Cancer Res 1993; 53: 2548–52

    PubMed  CAS  Google Scholar 

  18. Korbelik M. The role of nitric oxide in the response of solid tumors to photodynamic therapy [abstract]. Photochem Photobiol 1997; 65: 55S–6S

    Google Scholar 

  19. Kessel D, Luo Y. Mitochondrial photodamage and PDT-induced apoptosis. J Photochem Photobiol B 1998; 42: 89–95

    Article  PubMed  CAS  Google Scholar 

  20. Liu X, Kim CN, Yang J, et al. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 1996; 86: 147–57

    Article  PubMed  CAS  Google Scholar 

  21. Kluck RM, Martin SJ, Hoffman BM, et al. Cytochrome c activation of CPP32-like proteolysis plays a critical role in a xenopus cell-free apoptosis system. EMBO J 1997; 16: 4639–49

    Article  PubMed  CAS  Google Scholar 

  22. Korbelik M. Induction of tumor immunity by photodynamic therapy. J Clin Laser Med Surg 1996; 14: 329–34

    PubMed  CAS  Google Scholar 

  23. Allison BA, Pritchard PH, Levy JG. Evidence for low density lipoprotein receptor-mediated uptake of benzoporphyrin derivative. Br J Cancer 1994; 69: 833–9

    Article  PubMed  CAS  Google Scholar 

  24. Maziere JC, Morliere P, Santus R. The role of the low density lipoprotein receptor pathway in the delivery of lipophilic photosensitizers in the photodynamic therapy of tumors. J Photochem Photobiol B 1991; 8: 351–60

    Article  PubMed  CAS  Google Scholar 

  25. Soncin M, Polo L, Reddi E, et al. Effect of axial ligation and delivery system on the tumor-localising and -photosensitizing properties of Ge(IV)-octabutoxy-phthalocyanines. Br J Cancer 1995; 71: 727–32

    Article  PubMed  CAS  Google Scholar 

  26. Korbelik M. Low density lipoprotein receptor pathway in the delivery of photofrin: how much is it relevant for selective accumulation of the photosensitizer in tumors? J Photochem Photobiol B 1992; 12: 107–19

    Article  PubMed  CAS  Google Scholar 

  27. Kessel D. HPD: structure determinants of localization. In: Kessel D, editor. Photodynamic therapy of neoplastic diseases. Boca Raton (FL): CRC Press, 1990: 1–14

    Google Scholar 

  28. Berg K, Anholt H, Moan J, et al. Photobiological properties of haematoporphyrin diesters: evaluation of possible applications in photochemotherapy. J Photochem Photobiol B 1995; 20: 37–45

    Article  Google Scholar 

  29. Jori G. Tumour photosensitizers: approaches to enhance the selectivity and efficiency of photodynamic therapy. J Photochem Photobiol B 1996; 36: 87–93

    Article  PubMed  CAS  Google Scholar 

  30. Gerweck LE, Seetharaman K. Cellular pH gradient in tumor versus normal tissue: potential exploitation for the treatment of cancer. Cancer Res 1996; 56: 1194–8

    PubMed  CAS  Google Scholar 

  31. Barrett AJ, Kennedy JC, Jones RA, et al. The effect of tissue and cellular pH on the selective biodistribution of porphyrin-type photochemotherapeutic agents: a volumetric titration study. J Photochem Photobiol B 1990; 6: 309–23

    Article  PubMed  CAS  Google Scholar 

  32. Pottier R, Kennedy JC. The possible role of ionic species in selective biodistribution of photochemotherapeutic agents toward neoplastic tissue. J Photochem Photobiol B 1990; 8: 1–16

    Article  PubMed  CAS  Google Scholar 

  33. Mew D, Wat CK, Towers GHN, et al. Photoimmunotherapy: treatment of animal tumors with tumor-specific monoclonal antibody-porphyrin conjugates. J Immuol 1993; 130: 1473–7

    Google Scholar 

  34. Hasan T. Photosensitizer delivery mediated by macromolecular carrier systems. In: Henderson BW, Dougherty TJ, editors. Photodynamic therapy: basic principles and clinical applications. New York: Marcel-Dekker, 1992: 187–200

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  36. Sitnik TM, Henderson BW. The effect of fluence rate on tumor and normal tissue responses to photodynamic therapy. Photochem Photobiol 1998; 67: 462–6

    Article  PubMed  CAS  Google Scholar 

  37. Van Geel IPJ, Oppelaar H, Marijnissen JPA, et al. Influence of fractionation and fluence rate in photodynamic therapy with Photofrin or mTHPC. Radiat Res 1996; 145: 602–9

    Article  PubMed  Google Scholar 

  38. Gibson SL, VanDerMeid KR, Murant RS, et al. Effects of various photoradiation regimens on the antitumor efficacy of photodynamic therapy for R3230AC mammary carcinomas. Cancer Res 1990; 50: 7236–41

    PubMed  CAS  Google Scholar 

  39. Bellnier DA, Lin CW. Photosensitization and split-dose recovery in cultured human urinary bladder carcinoma cells containing nonexchangeable hematoporphyrin derivative. Cancer Res 1985; 45: 2507–11

    PubMed  CAS  Google Scholar 

  40. Bays R, Wagnieres G, Robert D, et al. Light dosimetry for photodynamic therapy in the esophagus. Lasers Surg Med 1997; 20: 290–303

    Article  PubMed  CAS  Google Scholar 

  41. Friauf WS, Smith PE, Russo A, et al. Light monitoring in photodynamic therapy. In: Nagle HT, Tomkins WJ, editors. IEEE case studies in medical instrument design. New York: IEEE, 1992: 127–38

    Google Scholar 

  42. Baas P, Murrer L, Zoetmulder FAN, et al. Photodynamic therapy as adjuvant therapy in surgically treated pleural malignancies. Br J Cancer 1997; 76: 819–26

    Article  PubMed  CAS  Google Scholar 

  43. Fenning MC, Brown DQ, Chapman JD. Photodosimetry of interstitial light delivery to solid tumors. Med Phys 1994; 21: 1149–56

    Article  PubMed  CAS  Google Scholar 

  44. Richter AM, Cerruti-Sola S, Sternberg ED, et al. Biodistribution of tritiated benzoporphyrin derivative (3H-BPD-MA): a new potent photosensitizer in normal and tumor-bearing mice. J Photochem Photobiol B 1990; 5: 231–44

    Article  PubMed  CAS  Google Scholar 

  45. Levy J. The preclinical and clinical development of Photofrin® and benzoporphyrin derivative: a reflection on opportunities and changes. J Photochem Photobiol B 1995; 30: 79–82

    Article  Google Scholar 

  46. Levy J, Chan A, Strong HA. The clinical status of benzoporphyrin derivative. Proc Int Soc Optical Engineering 1995; 2625: 86–95

    Google Scholar 

  47. Van Geel IPG, Oppelaar H, Oussoren YG, et al. Photosensitizing efficacy of mTHPC-PDT compared to Photofrin-PDT in the RIF-1 mouse tumour and normal skin. Int J Cancer 1995; 60: 388–94

    Article  PubMed  CAS  Google Scholar 

  48. Ronn AM, Lofgren LA, Westborn KM. Interspecies pharmacokinetics as applied to the “hard drug” photosensitizing agent meta (tetrahydroxylchlorin). Proc Int Soc Optical Engineering 1995; 2625: 118–23

    Google Scholar 

  49. Tralau CJ, Barr H, Sanderman R, et al. Aluminum sulfonated phthalocyanine distribution in rodent tumors of the colon, brain and pancreas. Photochem Photobiol 1987; 46: 777–81

    Article  PubMed  CAS  Google Scholar 

  50. Young SW, Qing F, Harriman A, et al. Gadolinium (III) texaphyrin: a tumor selective radiation sensitizer that is detectable by MRI. Proc Natl Acad Sci U S A 1996; 93: 6610–5

    Article  PubMed  CAS  Google Scholar 

  51. Yuen AR, Panella TJ, Wieman J, et al. Phase I trial of photodynamic therapy with lutetium lexaphyrin (LU-TEX) [abstract]. Proc Am Soc Clin Oncol 1997; 16: 219a

    Google Scholar 

  52. Regula J, MacRobert AJ, Gorchein A, et al. Photosensitisation and photodynamic therapy of oesophageal, duodenal, and colorectal tumours using 5 aminolaevulinic acid induced protoporphyrin IX: a pilot study. Gut 1995; 36: 67–75

    Article  PubMed  CAS  Google Scholar 

  53. Peng Q, Berg K, Moan J, et al. 5-aminolevulinic acid—based photodynamic therapy: principles and experimental research. Photochem Photobiol 1997; 65: 235–51

    Article  PubMed  CAS  Google Scholar 

  54. 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

    Article  PubMed  CAS  Google Scholar 

  55. Lightdale CJ, Heier SK, Marcon NE, et al. Photodynamic therapy with porfimer sodium versus thermal ablation therapy with Nd: YAG laser for palliation of esophageal cancer: a multicenter trial. Gastrointest Endosc 1995; 42: 507–12

    Article  PubMed  CAS  Google Scholar 

  56. Overholt BF, Panjehpour M. Photodynamic therapy for Barrett’s esophagus. Gastrointest Endosc Clin N Am 1997; 2: 207–20

    Google Scholar 

  57. Moghissi K, Dixon K, Parsons RJ. Acontrolled trial of Nd-YAG laser vs photodynamic therapy for advanced malignant bronchial obstruction. Lasers Med Sci 1993; 8: 269–73

    Article  Google Scholar 

  58. Cortese DA, Edell ES, Kinsey JH. Photodynamic therapy for early stage squamous cell carcinoma of the lung. Mayo Clin Proc 1997; 72: 595–602

    PubMed  CAS  Google Scholar 

  59. Pass HI, DeLaney TF, Tochner Z, et al. Intrapleural photodynamic therapy: results of a phase I trial. Ann Surg Oncol 1994; 1: 28–37

    Article  PubMed  CAS  Google Scholar 

  60. Benson RC. Laser photodynamic therapy for bladder cancer. Mayo Clin Proc 1986; 61: 859–64

    Article  PubMed  Google Scholar 

  61. Prout GR, Lin CW, Benson RC, et al. Photodynamic therapy with hematoporphyrin derivative in the treatment of superficial transitional-cell carcinoma of the bladder. N Engl J Med 1987; 317: 1251–5

    Article  PubMed  Google Scholar 

  62. Tsuchiya A, Obara N, Miwa M, et al. Hematoporphyrin derivative and laser photoradiation in the diagnosis and treatment of bladder cancer. J Urol 1983; 130: 79–82

    PubMed  CAS  Google Scholar 

  63. Hisazumi H, Misaki T, Miyoshi N. Photoradiation therapy of bladder tumors. J Urol 1983; 130: 685–7

    PubMed  CAS  Google Scholar 

  64. Chang SC, Buonaccorsi G, MacRobert A, et al. Interstitial and transurethral photodynamic therapy of the canine prostate using meso-tetra-(m-hydroxyphenyl) chlorin. Int J Cancer 1996; 67: 555–62

    Article  PubMed  CAS  Google Scholar 

  65. Wilson BD, Mang TS, Stoll H, et al. Photodynamic therapy for the treatment of basal cell carcinoma. Arch Dermatol 1992; 128: 1597–601

    Article  PubMed  CAS  Google Scholar 

  66. Kennedy JC, Pottier RH. Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy. J Photochem Photobiol B 1992; 6: 275–92

    Article  Google Scholar 

  67. 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

    Article  PubMed  CAS  Google Scholar 

  68. Cairnduff 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

    Article  PubMed  CAS  Google Scholar 

  69. Svanberg K, Andersson T, Killander D, et al. Photodynamic therapy of non-melanoma malignant tumours of the skin using topical 8-aminolevulinic acid sensitization and laser irradiation. Br J Dermatol 1994; 130: 743–51

    Article  PubMed  CAS  Google Scholar 

  70. Sperduto PW, DeLaney TF, Thomas G, et al. Photodynamic therapy for chest wall recurrence in breast cancer. Int J Radiat Oncol Biol Phys 1991; 21: 441–6

    Article  PubMed  CAS  Google Scholar 

  71. Gluckman JL. Hematoporphyrin photodynamic therapy: is there truly a future in head and neck oncology? Reflections on a 5-year experience. Laryngoscope 1991; 101: 36–42

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R. Alex Hsi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alex Hsi, R., Rosenthal, D.I. & Glatstein, E. Photodynamic Therapy in the Treatment of Cancer. Drugs 57, 725–734 (1999). https://doi.org/10.2165/00003495-199957050-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-199957050-00005

Keywords

Navigation