Photodynamic therapy – Introduction and Applications

Introduction into PDT (K. Plaetzer, T. Kiesslich)

modified from:
Plaetzer, K., T. Kiesslich, T. Verwanger and B. Krammer (2003).
The Modes of Cell Death Induced by PDT: An Overview.  Medical Laser Application 18(1): 7-19.,  view pdf

Since its introduction as a promising new method for cancer treatment about three decades ago, photodynamic therapy (PDT) has become progressively well-established as a mode of treatment of malignant (1-4) as well as non-malignant diseases (5-7) which are characterized by the occurrence of unwanted or harmful cells. Typically carried out as a two-step protocol, PDT covers selective uptake of the photosensitizing molecules by target cells and the subsequent irradiation with visible light of the appropriate wavelength for excitation of the photosensitizer (illustrated in Fig.1).

In the range of concentrations used for PDT the photosensitizing molecule is harmless per se, but upon absorption of a photon the molecule is energized into an excited singlet state where it may undergo intersystem crossing and end up in the relatively long-lasting triplet state. This triplet state can either exchange an electron or a hydrogen atom with adjacent molecules (type I photochemical reaction, indicated by “I” in the figure) or transfer energy to molecular oxygen in the ground state (type II photochemical reaction, indicated by “II” in the figure). The electron transfer reaction can produce superoxide anions, a process, which is usually followed by a conversion of superoxide anions to H202, the latter being an immediate precursor of the hydroxyl radical, the most dangerous member of the ROS family. The type II photochemical reaction generates singlet molecular oxygen (1O2), a highly reactive intermediate that interacts with many biomolecules, such as proteins, nucleic acids and lipids. In simple chemical systems most sensitizing molecules used in PDT have been shown to effectively produce 1O2, so the type II reaction seems to be dominant in PDT at least with porphyrins or porphyrin-like sensitizing molecules (8-12).
In general, the response of cells to damage depends on several factors which can be classified as external and internal parameters. In PDT, the treatment parameters, such as photosensitizer concentration and the light dose applied represent the most important external parameters, whilst the cellular metabolic state as well as the cell cycle phase can be named among major internal parameters influencing the sensitivity of cells to photodynamic treatment (13).

Applications of PDT

modified from:
Dougherty, T. J. (2002): An update on photodynamic therapy applications. J Clin Laser Med Surg 20(1): 3-7.  PUBMED

Photodynamic therapy, following health agency approvals throughout the world for various cancers and other diseases, is being accepted as a treatment to be added to the medical practitioner’s armamentarium. This can be partly attributed to the very attractive concept of PDT; the combination of two therapeutic agents, a photosensitizing drug and light, which are relatively harmless by themselves but combined (in the presence of oxygen) ultimately cause more or less selective target cell destruction. PDT has – except for an increased light sensitivity for a limited period of time – no side-effects in many cases. It can be applied locally and multiple treatments may be administered. Additionally PDT is a low-cost tumor therapy and very simple to use.
Oncologic indications approved by health agencies (or with approval pending) cover bladder cancer (14-16), esophageal cancer (17-20) as well as early and late stage lung cancer (21-24). Other oncology indications cover treatments of cancers of the oral cavity and the aerodigestive tract (25-28), skin cancer (29-33) prostate cancer (14, 34) and nonresectable cholangiocarcinoma (35). PDT is being investigated as adjuvant in the treatment of brain tumors (36-40), mesotheliomas (41-43) and intraperitoneal tumors (44-46).
Nononcologic applications of PDT are actinic keratosis (47, 48), age-related macular degeneration (49-51) and coronary artery disease (52-54) and restenosis (55, 56).
Research on PDT is still sustained; new applications will be explored.


1. Dougherty, T.J., Photodynamic therapy. Photochem Photobiol, 1993. 58(6): p. 895-900.  PUBMED
2. Hsi, R.A., D.I. Rosenthal, and E. Glatstein, Photodynamic therapy in the treatment of cancer: current state of the art. Drugs, 1999. 57(5): p. 725-34.  PUBMED
3. Sibata, C.H., et al., Photodynamic therapy in oncology. Expert Opin Pharmacother, 2001. 2(6): p. 917-27.  PUBMED
4. Wilson, B.C., Photodynamic therapy for cancer: principles. Can J Gastroenterol, 2002. 16(6): p. 393-6.  PUBMED
5. Levy, J.G. and M. Obochi, New applications in photodynamic therapy. Introduction. Photochem Photobiol, 1996. 64(5): p. 737-9.  PUBMED
6. Dougherty, T.J., An update on photodynamic therapy applications. J Clin Laser Med Surg, 2002. 20(1): p. 3-7.  PUBMED
7. Szeimies, R.M., M. Landthaler, and S. Karrer, Non-oncologic indications for ALA-PDT. J Dermatolog Treat, 2002. 13 Suppl 1: p. S13-8.  PUBMED
8. Weishaupt, K.R., C.J. Gomer, and T.J. Dougherty, Identification of singlet oxygen as the cytotoxic agent in photoinactivation of a murine tumor. Cancer Res, 1976. 36(7 PT 1): p. 2326-9.  PUBMED
9. Halliwell, B. and J.M. Gutteridge, Free radicals, lipid peroxidation, and cell damage. Lancet, 1984. 2(8411): p. 1095.  PUBMED

10. Agarwal, R., et al., Evidence for the involvement of singlet oxygen in the photodestruction by chloroaluminum phthalocyanine tetrasulfonate. Biochem Biophys Res Commun, 1990. 173(1): p. 34-41.  PUBMED
11. Henderson, B.W. and T.J. Dougherty, How does photodynamic therapy work? Photochem Photobiol, 1992. 55(1): p. 145-57.  PUBMED
12. Moore, J.V., C.M. West, and C. Whitehurst, The biology of photodynamic therapy. Phys Med Biol, 1997. 42(5): p. 913-35.  PUBMED
13. Wyld, L., M.W. Reed, and N.J. Brown, Differential cell death response to photodynamic therapy is dependent on dose and cell type. Br J Cancer, 2001. 84(10): p. 1384-6.  PUBMED
14. Chang, S.C. and S.G. Bown, Photodynamic therapy: applications in bladder cancer and other malignancies. J Formos Med Assoc, 1997. 96(11): p. 853-63.  PUBMED
15. Nseyo, U.O., et al., Photodynamic therapy (PDT) in the treatment of patients with resistant superficial bladder cancer: a long-term experience. J Clin Laser Med Surg, 1998. 16(1): p. 61-8.  PUBMED
16. Nseyo, U.O., Photodynamic therapy in the management of bladder cancer. J Clin Laser Med Surg, 1996. 14(5): p. 271-80.  PUBMED
17. Lightdale, C.J., et al., Photodynamic therapy with porfimer sodium versus thermal ablation therapy with Nd:YAG laser for palliation of esophageal cancer: a multicenter randomized trial. Gastrointest Endosc, 1995. 42(6): p. 507-12.  PUBMED
18. Gossner, L., Photodynamic therapy: esophagus. Can J Gastroenterol, 2002. 16(9): p. 642-4.  PUBMED
19. Barr, H., C. Kendall, and N. Stone, Photodynamic therapy for esophageal cancer: a useful and realistic option. Technol Cancer Res Treat, 2003. 2(1): p. 65-76.  PUBMED
20. Greenwald, B.D., Photodynamic therapy for esophageal cancer. Update. Chest Surg Clin N Am, 2000. 10(3): p. 625-37.  PUBMED

21. Lam, S., Photodynamic therapy of lung cancer. Semin Oncol, 1994. 21(6 Suppl 15): p. 15-9.  PUBMED
22. Sutedja, T.G. and P.E. Postmus, Photodynamic therapy in lung cancer. A review. J Photochem Photobiol B, 1996. 36(2): p. 199-204.  PUBMED, fullText
23. Ost, D., Photodynamic therapy in lung cancer. Oncology (Huntingt), 2000. 14(3): p. 379-86, 391; discussion 391-2, 395.  PUBMED
24. Ost, D., Photodynamic therapy in lung cancer. A review. Methods Mol Med, 2003. 75: p. 507-26.  PUBMED
25. Kubler, A.C., M. Scheer, and J.E. Zoller, Photodynamic therapy of head and neck cancer. Onkologie, 2001. 24(3): p. 230-7.  PUBMED
26. Fan, K.F., et al., Photodynamic therapy using mTHPC for malignant disease in the oral cavity. Int J Cancer, 1997. 73(1): p. 25-32.  PUBMED
27. Biel, M.A., Photodynamic therapy and the treatment of neoplastic diseases of the larynx. Laryngoscope, 1994. 104(4): p. 399-403.  PUBMED
28. Biel, M.A., Photodynamic therapy and the treatment of head and neck cancers. J Clin Laser Med Surg, 1996. 14(5): p. 239-44. PUBMED
29. Szeimies, R.M., et al., Topical photodynamic therapy in dermatology. J Photochem Photobiol B, 1996. 36(2): p. 213-9.  PUBMED,  fullText
30. Morton, C.A., The emerging role of 5-ALA-PDT in dermatology: is PDT superior to standard treatments? J Dermatolog Treat, 2002. 13 Suppl 1: p. S25-9.  PUBMED

31. Zeitouni, N.C., A.R. Oseroff, and S. Shieh, Photodynamic therapy for nonmelanoma skin cancers. Current review and update. Mol Immunol, 2003. 39(17-18): p. 1133-6.  PUBMED,  fullText
32. Szeimies, R.M. and M. Landthaler, Photodynamic therapy and fluorescence diagnosis of skin cancers. Recent Results Cancer Res, 2002. 160: p. 240-5.  PUBMED
33. Kurwa, H.A. and R.J. Barlow, The role of photodynamic therapy in dermatology. Clin Exp Dermatol, 1999. 24(3): p. 143-8.  PUBMED,  fullText
34. Muschter, R., Photodynamic therapy: a new approach to prostate cancer. Curr Urol Rep, 2003. 4(3): p. 221-8.  PUBMED
35. Ortner, M.A., et al., Photodynamic therapy of nonresectable cholangiocarcinoma. Gastroenterology, 1998. 114(3): p. 536-42.  PUBMED
36. Popovic, E.A., A.H. Kaye, and J.S. Hill, Photodynamic therapy of brain tumors. J Clin Laser Med Surg, 1996. 14(5): p. 251-61.  PUBMED
37. Muller, P.J. and B.C. Wilson, Photodynamic therapy for malignant newly diagnosed supratentorial gliomas. J Clin Laser Med Surg, 1996. 14(5): p. 263-70.  PUBMED

38. Muller, P.J. and B.C. Wilson, Photodynamic therapy for recurrent supratentorial gliomas. Semin Surg Oncol, 1995. 11(5): p. 346-54.  PUBMED
39. Goodell, T.T. and P.J. Muller, Photodynamic therapy: a novel treatment for primary brain malignancy. J Neurosci Nurs, 2001. 33(6): p. 296-300.  PUBMED
40. Kaye, A.H. and J.S. Hill, Photodynamic therapy of brain tumours. Ann Acad Med Singapore, 1993. 22(3 Suppl): p. 470-81.  PUBMED
41. Moskal, T.L., et al., Operation and photodynamic therapy for pleural mesothelioma: 6-year follow-up. Ann Thorac Surg, 1998. 66(4): p. 1128-33.  PUBMED
42. Pass, H.I., et al., Phase III randomized trial of surgery with or without intraoperative photodynamic therapy and postoperative immunochemotherapy for malignant pleural mesothelioma. Ann Surg Oncol, 1997. 4(8): p. 628-33.  PUBMED
43. Pass, H.I. and J.S. Donington, Use of photodynamic therapy for the management of pleural malignancies. Semin Surg Oncol, 1995. 11(5): p. 360-7.  PUBMED
44. Griffin, G.M., et al., Preclinical evaluation of motexafin lutetium-mediated intraperitoneal photodynamic therapy in a canine model. Clin Cancer Res, 2001. 7(2): p. 374-81.  PUBMED,  fullText

45. Tochner, Z.A., Photodynamic therapy for peritoneal carcinomatosis. Cancer Treat Res, 1994. 70: p. 83-91.  PUBMED
46. DeLaney, T.F., et al., Phase I study of debulking surgery and photodynamic therapy for disseminated intraperitoneal tumors. Int J Radiat Oncol Biol Phys, 1993. 25(3): p. 445-57.  PUBMED
47. Goldman, M. and D. Atkin, ALA/PDT in the treatment of actinic keratosis: spot versus confluent therapy. J Cosmet Laser Ther, 2003. 5(2): p. 107-10.  PUBMED
48. Jeffes, E.W., Levulan: the first approved topical photosensitizer for the treatment of actinic keratosis. J Dermatolog Treat, 2002. 13 Suppl 1: p. S19-23.  PUBMED
49. Messmer, K.J. and S.R. Abel, Verteporfin for age-related macular degeneration. Ann Pharmacother, 2001. 35(12): p. 1593-8.  PUBMED,  fullText

50. Rechtman, E., et al., An update on photodynamic therapy in age-related macular degeneration. Expert Opin Pharmacother, 2002. 3(7): p. 931-8.  PUBMED,  fullText
51. Koh, A.H. and C.L. Ang, Age-related macular degeneration: what´s new. Ann Acad Med Singapore, 2002. 31(3): p. 399-404.  PUBMED
52. Yamaguchi, A., et al., Photodynamic therapy with motexafin lutetium (Lu-Tex) reduces experimental graft coronary artery disease. Transplantation, 2001. 71(11): p. 1526-32.  PUBMED,  fullText
53. Jenkins, M.P., et al., Reduction in the response to coronary and iliac artery injury with photodynamic therapy using 5-aminolaevulinic acid. Cardiovasc Res, 2000. 45(2): p. 478-85.  PUBMED,  fullText
54. Sluiter, W., et al., Prevention of late lumen loss after coronary angioplasty by photodynamic therapy: role of activated neutrophils. Mol Cell Biochem, 1996. 157(1-2): p. 233-8.  PUBMED
55. Krammer, B., Vascular effects of photodynamic therapy. Anticancer Res, 2001. 21(6B): p. 4271-7.  PUBMED
56. Rockson, S.G., et al., Photoangioplasty: An emerging clinical cardiovascular role for photodynamic therapy. Circulation, 2000. 102(5): p. 591-6.  PUBMED,  fullText