Lung Cancer pp 507-526 | Cite as

Photodynamic Therapy in Lung Cancer

A Review
  • David Ost
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 75)


Photodynamic therapy (PDT) involves the use of photosensitizing agents for treatment of malignant disease. These photosensitizing agents are infused intravenously and are selectively retained within tumor cells. The agents remain inactive until exposed to light of the proper wavelength. When activated by light, these compounds generate toxic oxygen radicals that result in tumor necrosis. Although several institutions worked with PDT in the 1980s, its use in the United States remained limited to research. More recently, PDT using the first FDA approved photosensitizing agent, porfimer sodium (Photofrin), has become available for routine clinical use in the United States.


Membrane Injury Advanced Lung Cancer Hematoporphyrin Derivative Photosensitize Agent Porfimer Sodium 
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.


  1. 1.
    Jesionek, A and Tappeiner, V. H. (1903) Zur behandlung der hautcarcinomit mit fluoresceirenden stoffen. Muench Med. Wochneshr. 47, 2042.Google Scholar
  2. 2.
    Figge, F H. J., Weiland, G. S., and Manganiello, L. O. J. (1948) Cancer detection and therapy. Affinity of neoplastic embryonic and traumatized tissue for porphyrins and metalloporphyrins. Proc. Soc. Exp. Biol. Med. 68, 640.PubMedGoogle Scholar
  3. 3.
    Auber, H. and Banger, G. (1942) Untersuchungen uber die Rolle der Porphyrine bei geschwulstkranken Menschen und tieren. Z. Krebsforsch 53, 65.CrossRefGoogle Scholar
  4. 4.
    Lipson, R. L. and Baldes, E. J. (1960) The photodynamic properties of a particular hematoporphyrin derivative. Arch. Dermatol. 82, 508.PubMedCrossRefGoogle Scholar
  5. 5.
    Lipson, R. L. and Baldes, E. J. (1961) The use of a derivative of hematoporphyrin in tumor detection. J. Natl. Cancer Inst. 26, 1.PubMedGoogle Scholar
  6. 6.
    Gray, M., Lipson, R. L., Mack, J. V. S., et al. (1967) Use of hematoporphyrin derivative in detection and management of cervical cancer. Am. J. Obstet. Gynecol. 9, 766.Google Scholar
  7. 7.
    Gregorie, H. G. Jr., Horger, E. O., Ward, J. L., et al. (1968) Hematoporphyrin-derivative fluorescence I malignant neoplasms. Ann. Surg. 167, 820–828.PubMedCrossRefGoogle Scholar
  8. 8.
    Lipson, R. L. and Baldes, E. J. (1961) The hematoporphyrin derivative: A new aid for endoscopic detection of malignant disease. J. Thorac. Cardiovasc. Surg. 42, 623.PubMedGoogle Scholar
  9. 9.
    Kelly, J. F., Snell, M. E., and Berenbaum, M. C. (1975) Photodynamic destruction of human bladder carcinoma. Br. J. Cancer 31, 237–244.PubMedCrossRefGoogle Scholar
  10. 10.
    Lipson, R. L., Gray, M. J., and Baldes, E. J. (1966) Hematoporphyrin derivative for detection and management of cancer. Proc. 9th Int. Cancer Cong. Tokyo, Japan 393.Google Scholar
  11. 11.
    Dougherty, T. J., Kaufman, J. E., Goldfarb, A., et al. (1978) Photoradiationtherapy for the treatment of malignant tumors. Cancer Res. 38, 2628–2635.PubMedGoogle Scholar
  12. 12.
    Dougherty, T. J. (1974) Activated dyes as antitumor agents. J. Natl. Cancer Inst. 51, 1333–1336.Google Scholar
  13. 13.
    Dougherty, T. J. (1984) Photoradiation therapy. Urol. Suppl. 23, 61.CrossRefGoogle Scholar
  14. 14.
    Christensen, T., Moan, J., Smedshammer, L., et al. (1985) Influence of hematoporphyrin derivative (HPD) and light on the attachment of cells to the substratum. Photochem. Photobiophys. 10, 53.Google Scholar
  15. 15.
    Denstaman, S. C., Dillehay, L. E., and Williams, J. R. (1985) Enhanced susceptibility of HPD-sensitized phototoxicity and correlated resistance to trypsin detachment in SV40 transformed IMR-90 cell. Photochem. Photobiophys. 10, 53.Google Scholar
  16. 16.
    Pass, H. I. (1993) Photodynamic therapy in oncology: mechanism and clinical use. J. Natl. Canc Inst. 85, 443–456.CrossRefGoogle Scholar
  17. 17.
    Salet, C. (1986) Hematoporphyrin and hematoporphyrin-derivative photosensitization of mitochondria. Biochimie 68, 865–868.PubMedCrossRefGoogle Scholar
  18. 18.
    Murant, R. S., Gibson, S. L., and Hilf, R. (1987) Photosensitizing effects of photofrin II on the site-selected mitochondrial enzymes adenylate kinase and monoamine oxidase. Cancer Res. 47, 4323–4328.PubMedGoogle Scholar
  19. 19.
    Dougherty, T. J., Gomer, C. J., Henderson, B. W., et al. (1998) Photodynamic therapy. J. Natl. Cancer Inst. 90(12), 889–905.PubMedCrossRefGoogle Scholar
  20. 20.
    Kessel, D. (1986) Sites of photosensitization by derivativesof hematoporphyrin. Photochem. Photobiol. 44, 489–93.PubMedCrossRefGoogle Scholar
  21. 21.
    Volden, G., Christensen, T., and Moan, J. (1981) Photodynamic membrane damage of hematoporphyrin derivative-treated NHIK 3025 cells in vitro. Photochem. Photobiophys. 3, 105.Google Scholar
  22. 22.
    Hilf, R., Smail, D. B., and Murant, R. S. (1984) Hematoporphyrin derivative-induced photosensitivity of mitochondrial succinate dehydrogenase and selected cytosolic enzymes of R3230AC mammary adenocarcinomas of rats. Cancer Res. 44, 1483–1488.PubMedGoogle Scholar
  23. 23.
    Hilf, R., Murant, R. S., Narayanan, U., et al. (1986) Relationship of mitochondrial function and cellular adenosine triphosphate levels to hematoporphyrin derivative-induced photosensitization in R3230AC mammary tumors. Cancer Res. 46, 211–217.PubMedGoogle Scholar
  24. 24.
    Mattiello, J., Evelhoch, J. L., Brown, E., et al. (1990) Effect of photodynamic therapy on RIF-1 tumor metabolism and blood flow examined by 31P and 2H NMR spectroscopy. NMR Biomed. 3, 64–70.PubMedCrossRefGoogle Scholar
  25. 25.
    Dodd, N. J., Moore, J. V., Poppitt, D. G., et al. (1989) In vivo magnetic resonance imaging of the effects of photodynamic therapy. Br. J. Cancer 60, 164–67.PubMedCrossRefGoogle Scholar
  26. 26.
    Gomer, C. J., Rucker, N., Banerjee, A., et al. (1983) Comparison of mutagenicity and induction of sister chromatid exchange in Chinese hamster cells exposed to hematoporphyrin derivative, ionizing radiation, or ultraviolet radiation. Cancer Res. 43, 2622–2627.PubMedGoogle Scholar
  27. 27.
    Lee See, K., Forbes, I. J., and Betts, W. H. (1984) Oxygen dependency of photocytotoxicity with haematoporphyrin derivative. Photochem. Photobiol. 39, 631–634.Google Scholar
  28. 28.
    Mitchell, J. B., McPherson, S., DeGraff, W., et al. (1985) Oxygen dependence of hematoporphyrin derivative-induced photoinactivation of Chinese hamster cells. Cancer Res. 45, 2008–2011.PubMedGoogle Scholar
  29. 29.
    Foote, C. S. (1984) Mechanisms of photooxygenation, in Porphyrin Localization and Treatment of Tumors (Doiron, D. R. and Gomer, C. J., eds.), Alan R. Liss, New York, pp. 3.Google Scholar
  30. 30.
    Rizzoni, W. E., Matthews, K., Pass, H. I., et al. (1987) In vitro photodynamic therapy of human lung cancer. Influence of dose rate, hematoporphyrin concentration and incubation, and cellular targets. Surg. Forum 38, 452–455.Google Scholar
  31. 31.
    Edell, E. S. and Cortese, D. A. (1995) Photodynamic therapy. Its use in the management of bronchogenic carcioma. Clin. Chest Med. 16(3), 455–463.PubMedGoogle Scholar
  32. 32.
    Wieman, T. J., Mang, T. S., Fingar, V. S., et al. (1988) Effects of photodynamic therapy on blood flow in normal and tumor vessels. Surgery 104, 512–517.PubMedGoogle Scholar
  33. 33.
    Stern, S. J., Flock, S., Small, S., et al. (1991) Chloraluminum sulphonated phthalocyanine versus dihematoporphyrin ether: early vascular events in the rat window chamber. Laryngoscope 101, 1219–1225.PubMedCrossRefGoogle Scholar
  34. 34.
    Ceckler, T. L., Gibson, S. L., Hilf, R., et al. (1990) I situ assessment of tumor vascularity using flourine NMR imaging. Magn. Reson. Med. 13, 416–433.PubMedCrossRefGoogle Scholar
  35. 35.
    Ben-Hur, E. and Orenstein, A. (1991) The endothelium and red blood cells as potential targets in PDT-induced vascular stasis. Int. J. Radiat. Biol. 60, 293–301.PubMedCrossRefGoogle Scholar
  36. 36.
    Fingar, V. H., Wieman, T. H., and Doak, K. W. (1990) Role of thromboxane and prostacycline release on photodynamic therapy-induced tumor destruction. Cancer Res. 50, 2599–2603.PubMedGoogle Scholar
  37. 37.
    Bugelski, P. H., Porter, C. W., and Dougherty, T. J. (1981) Autoradiographic distribution of hematoporphyrin derivative in normal and tumor tissue of the mouse. Cancer Res. 41, 4606–4612.PubMedGoogle Scholar
  38. 38.
    Barel, A., Jori, G., Perin, A., et al. (1986) Role of high-, low-, and very low-density lipoproteins in the transport and tumor-delivery of hematoporphyrin in vivo. Cancer Lett. 32, 145–150.PubMedCrossRefGoogle Scholar
  39. 39.
    Pass, H. I. (1991) Photodynamic therapy for lung cancer. Chest Surg. Clin. North Am. 1, 135–151.Google Scholar
  40. 40.
    Moan, J. (1990) Properties for optimal PDT sensitizers. J. Photochem. Photobiol. 5, 521–524.CrossRefGoogle Scholar
  41. 41.
    Matthews, W., Cook, J., Mitchell, J. B., et al. (1989) In vitro photodynamic therapy of human lung cancer: inverstigation of dose-rate effects. Cancer Res. 49, 1718–1721.PubMedGoogle Scholar
  42. 42.
    Foster, T. H., Gibson, S. L., Gao, L., et al. (1992) Analysis of photochemical oxygen consumption effects on photodynamic therapy. Proc. Int. Soc. Optical Engin. (SPIE) 1645, 104–114.Google Scholar
  43. 43.
    Kato, H. and Cortese, D. A. (1985) Early detection of lung cancer by means of hematoporphyrin derivative fluorescence and laser photoradiation. Clin. Chest Med. 6, 237–53.PubMedGoogle Scholar
  44. 44.
    Kato, H., Imaizumi, T., Aisawa, K., et al. (1990) Photodynamic diagnosis in respiratory tract malignancy using excimer laser system. J. Photochem. Photobiol. 6, 189–196.CrossRefGoogle Scholar
  45. 45.
    King, E. G., Man, G., Riche, J., et al. (1982) Fluorescence bronchoscopy in the localization of bronchogenic carcinoma. Cancer 49, 777–782.PubMedCrossRefGoogle Scholar
  46. 46.
    Edell, E. S. and Cortese, D. A. (1992) Photodynamic therapy in the management of early superficial squamous cell carcinoma as an alternative to surgical resection. Chest 102, 1319–1322.PubMedCrossRefGoogle Scholar
  47. 47.
    Kato, H., Okunaka, T., and Shimatani, H. (1996) Photodynamic therapy for early stage bronchogenic carcinoma. J. Clin. Laser Med. Surg. 14, 235–238.PubMedGoogle Scholar
  48. 48.
    Furuse, K., Fukuoka, M., Kato, H., et al. (1993) Prospective phase II study on photodynamic therapy with photofrin II for centrally located early-stage lung cancer. The Japan lung center. J. Clin. Oncol. 11, 1852–1857.PubMedGoogle Scholar
  49. 49.
    Sutedja, T., Lam, S., LeRiche, J. C., et al. (1994) Response and pattern of failure after photodynamic therapy for intraluminal stage I lung cancer. J. Bronchology 1, 295–298.CrossRefGoogle Scholar
  50. 50.
    Cortese, D. A., Edell, E. S., and Kinsey, J. H. (1997) Photodynamic therapy for early stage squamous cell carcinoma. Mayo Clin. Proc. 72, 595–602.PubMedGoogle Scholar
  51. 51.
    Marijnissen, J. P. A., Baas, P., Beek, J. F., et al. (1993) Pilot study on light dosimetry for endobronchial photodynamic therapy. Photochem. Photobiol. 58, 92–99.PubMedCrossRefGoogle Scholar
  52. 52.
    Hayata, Y., Kato, H., Konaka, C., et al. (1982) Hematoporphyrin derivative and laser photoradiation in the treatment of lung cancer. Chest 81, 269–277.PubMedCrossRefGoogle Scholar
  53. 53.
    Woolner, L. B., Fontana, R. S., and Cortese, D. A. (1984) Roentgenographically occult lung cancer: Pathologic findings and frequency of multicentricity during a 10-year period. Mayo Clin. Proc. 59, 453–466.PubMedCrossRefGoogle Scholar
  54. 54.
    Nagamoto, N., Saito, Y., Ohta, S., et al. (1989) Relation of lymph node metastasis to primary tumor size and microscopic appearance of roentgengraphically occult lung cancer. Am. J. Surg. Pathol. 13, 1009–1013.PubMedCrossRefGoogle Scholar
  55. 55.
    Moghissi, K., Dixon, K., Stringer, M., et al. (1999) The place of bronchoscopic photodynamic therapy in advanced unresectable lung cancer: experience of 100 cases. Eur. J. Cardthorac. Surg. 15(1), 1–6.CrossRefGoogle Scholar
  56. 56.
    McCaughan, J. S. Jr. (1996) Photodynamic therapy of endobronchial and esophageal tumors: An overview: J. Clin. Laser Med. Surg. 14(5), 223–233.PubMedGoogle Scholar
  57. 57.
    Lam, S., Crofton, C., and Cory, P. (1991) Combined photodynamic therapy (PDT) using Photofrin and radiotherapy (XRT) versus radiotherapy alone in patients with inoperable distribution non-small cell bronchogenic cancer. Proc. Intl. Soc. Optical Engin. (SPIE) 20–28.Google Scholar
  58. 58.
    Moghissi, K., Dixon, K., and Parsons, R. J. (1993) A controlled trial of Nd-YAG vs Photodynamic therapy for advanced malignant bronchial obstruction. Lasers Med. Sci. 8, 269–273.CrossRefGoogle Scholar
  59. 59.
    Diz-Jimenez, J. P., Martinez-Ballarin, J. E., Llunell, E., et al. (1999) Efficacy and safety of photodynamic therapy versus Nd-YAG laser resection in NSCLC with airway obstruction. Eur. Respir. J. 14, 800–805.CrossRefGoogle Scholar
  60. 60.
    Shah, S. and Ost, D. (2000) Photodynamic therapy: a case series demonstrating its role in patients receiving mechanical ventilation. Chest 118(5), 1419–1423.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2003

Authors and Affiliations

  • David Ost
    • 1
  1. 1.North Shore University Hospital and New York University School of MedicineManhasset

Personalised recommendations