Skip to main content

Advertisement

SpringerLink
Log in

The use of 5-aminolaevulinic acid as a photosensitiser in photodynamic therapy and photodiagnosis

  • Published:
Photochemical & Photobiological Sciences Aims and scope Submit manuscript

Abstract

Photodynamic therapy (PDT) is a treatment for cancer and pre-malignant conditions, which involves the administration of a photosensitising agent followed by exposure of the tissue to light. 5-Aminolaevulinic acid (ALA) is a naturally occurring compound in the haem biosynthetic pathway, which is metabolised to a photosensitive product, protoporphyrin IX (PpIX). The major advantage of ALA when compared to synthetic photosensitisers is the rapid metabolism, which significantly reduces the period of cutaneous photosensitivity. This review focuses on the development of ALA as a photosensitiser in photodynamic therapy and photodiagnosis, and the wide range of clinical applications in which ALA is now being used as a therapeutic modality.

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. K. R. Weishaupt, C. J. Gomer and T. J. Dougherty, Identification of singlet oxygen as the cytotoxic agent in photo-inactivation of a murine tumour, Cancer Res., 1976, 36, 2326–2329.

    CAS  PubMed  Google Scholar 

  2. J. J. Wieman and V. H. Fingar, Photodynamic Therapy, Lasers Gen. Surg., 1992, 72, 609–622.

    CAS  Google Scholar 

  3. B. W. Henderson and T. J. Dougherty, How does photodynamic therapy work?, Photochem. Photobiol., 1992, 55, 145–57.

    Article  CAS  PubMed  Google Scholar 

  4. D. L. Drabkin, Introduction: Some historical highlights in knowledge of porphyrins and porphyrias, Ann. N. Y. Acad. Sci., 1963, 104, 658.

    Article  Google Scholar 

  5. S. Granick, Hepatic porphyria and drug-induced or chemical porphyria, Ann. N. Y. Acad. Sci., 1965, 123, 188.

    Article  CAS  PubMed  Google Scholar 

  6. D. X. G. Divaris, J. C. Kennedy and R. H. Pottier, Phototoxic damage to sebaceous glands and hair follicles of mice after systemic administration of 5-aminolaevulinic acid correlates with localized protoporphyrin production, Am. J. Pathol., 1990, 136, 891–897.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. G. H. Elder, Haem synthesis and the porphyrias, in Scientific Foundations of Clinical Biochemistry, ed. D. L. Williams and V. Marks, Heineman, London, pp. 175-186.

  8. J. C. Kennedy and R. H. Pottier, Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy, J. Photochem. Photobiol., B, 1992, 14, 275–292.

    Article  CAS  Google Scholar 

  9. C. Rimington, Porphyrin and haem biosynthesis and its control, Acta Med. Scand., 1966, 179(suppl. 445), 11–24.

    Google Scholar 

  10. J. Marriott, Regulation of porphyrin synthesis, Biochem. Soc. Symp., 1968, 28, 61–74.

    CAS  PubMed  Google Scholar 

  11. R. H. Pottier, Y. F. A. Chow, J.-P. La Plante, T. G. Truscott, J. C. Kennedy and L A. Beiner, Non-invasive technique for obtaining fluorescence excitation and emission spectra in vivo, Photochem. Photobiol., 1986, 44, 679–687.

    Article  CAS  PubMed  Google Scholar 

  12. Z. Malik and M. Djaldetti, 5-aminolevulinic acid stimulation of porphyrin and hemoglobin synthesis by uninduced Friend erythroleukemic cells, Cell Differ., 1979, 8, 223–233.

    Article  CAS  PubMed  Google Scholar 

  13. A. A. F. Sima, J. C. Kennedy, D. Balkeslee and D. M. Robertson, Experimental porphyric neuropathy: a preliminary report, Can. J. Neurol. Sci., 1981, 8, 105–114.

    Article  CAS  PubMed  Google Scholar 

  14. C. S. Loh, D. I. Vernon, A. J. MacRobert, J. Bedwell, S. G. Bown and S. B. Brown, Endogenous porphyrin distribution induced by 5-aminolaevulinic acid in the tissue layers of the gastrointestinal tract, J. Photochem. Photobiol., B, 1993, 20, 47–54.

    Article  CAS  Google Scholar 

  15. R. Ackroyd, N. J. Brown, D. I. Vernon, D. J. H. Roberts, T. J. Stephenson, S. L. Marcus, C. J. Stoddard and M. W. R. Reed, 5-aminolevulinic acid photosensitisation of dysplastic Barrett’s esophagus: a pharmacokinetic study, Photochem. Photobiol., 1999, 70, 656–662.

    CAS  PubMed  Google Scholar 

  16. Z. Malik and H. Lugaci, Destruction of erythroleukaemic cells by photoactivation of endogenous porphyrins, Br. J. Cancer, 1987, 56, 589–595.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. C. S. Loh, A. J. MacRobert, J. Bedwell, J. Regula, N. Krasner and S. G. Bown, Oral versus intravenous administration of 5-aminolaevulinic acid for photodynamic therapy, Br. J. Cancer, 1993, 68, 41–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. J. Leveckis, J. L. Burn, N. J. Brown and M. W. R. Reed, Kinetics of endogenous protoporphyrin IX induction by aminolaevulinic acid: preliminary studies in the bladder, J. Urol., 1994, 152, 550–553.

    Article  CAS  PubMed  Google Scholar 

  19. L. Wyld, J. L. Burn, M. W. R. Reed and N. J. Brown, Factors affecting aminolaevulinic acid-induced generation of protoporphyrin IX, Br. J. Cancer, 1997, 76, 705–712.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. T. S. Mang, T. J. Dougherty, W. R. Potter, D. G. Boyle, S. Somer and J. Moan, Photobleaching of porphyrins used in photodynamic therapy and implications for therapy, Photochem. Photobiol., 1987, 45, 501–506.

    Article  CAS  PubMed  Google Scholar 

  21. J. Moan, Effect of bleaching of porphyrin sensitizers during photodynamic therapy, Cancer Lett., 1986, 33, 45–53.

    Article  CAS  PubMed  Google Scholar 

  22. H. H. Inhoffen, H. Brockmann and K. M. Bliesener, Photoprotoporphyrine und ihre Umwandlung in Spirographis- sowie Isospiro-graphis-porphyrin, Justus Liebigs Ann. Chem., 1969, 730, 173–185.

    Article  CAS  Google Scholar 

  23. P. Juzenas, V. Iani, S. Bagdonas, R. Rotomskis and J. Moan, Fluorescence spectroscopy of normal mouse skin exposed to 5-aminolaevulinic acid and red light, J. Photochem. Photobiol., B, 2001, 61, 78–86.

    Article  CAS  Google Scholar 

  24. N. I. Berlin, A. Neuberger and J. J. Scott, The metabolism of delta-aminolaevulinic acid. 1. Normal pathways, studied with the aid of 15N, Biochem. J., 1956, 64, 80–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. N. I. Berlin, A. Neuberger and J. J. Scott, The metabolism of delta-aminolaevulinic acid. 2. Normal pathways studied with the aid of 14C, Biochem. J., 1956, 64, 90–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. W. E. Grant, C. Hopper, A. J. MacRobert, P. M. Speight and S. G. Bown, Photodynamic therapy of oral cancer: photosensitisation with systemic aminolaevulinic acid, Lancet, 1993, 342, 147–148.

    Article  CAS  PubMed  Google Scholar 

  27. P. Qian, J. F. Evensen, C. Rimington and J. Moan, A comparison of different photosensitizing dyes with respect to uptake C3H-tumors and tissues of mice, Cancer Lett., 1987, 36, 1–10.

    Article  CAS  PubMed  Google Scholar 

  28. N. R. Boucher, N. J. Brown and M. W. R. Reed, Microcirculatory effects of aminolaevulinic acid (ALA)-induced protoporphyrin IX (Pp IX)-mediated photodynamic therapy (PDT) in vivo, Br. J. Cancer, 1995, 72(Suppl. XXV), 23.

    Google Scholar 

  29. S. R. Edwards, B. C. Shanley and J. A. Reynoldson, Neuropharmacology of delta-aminolaevulinic acid-I. Effect of acute administration in rodents, Neuropharmacology, 1984, 23, 477–481.

    Article  CAS  PubMed  Google Scholar 

  30. P. Mustajoki, K. Timonen, A. Gorchein, A. M. Seppalainen, E. Matikainen and R. Tenhunen, Sustained high plasma 5-aminolaevulinic acid concentration in a volunteer: no porphyric symptoms, Eur. J. Clin. Invest., 1992, 22, 407–411.

    Article  CAS  PubMed  Google Scholar 

  31. J. Bedwell, A. J. MacRobert, D. Phillips and S. G. Bown, Fluorescence distribution and photodynamic effect of ALA-induced PpIX in the DMH rat colonic tumour model, Br. J. Cancer, 1992, 65, 818–824.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. H. Barr, N. A. Shepherd, A. Dix, D. J. Roberts, W. C. Tan and N. Krasner, Eradication of high-grade dysplasia in columnar-lined (Barrett’s) oesophagus by photodynamic therapy with endogenously generated protoporphyrin IX, Lancet, 1996, 348, 584–585.

    Article  CAS  PubMed  Google Scholar 

  33. J. Moan and T. Christensen, Porphyrins as tumor localization agents and their possible use in photochemotherapy of cancer, Tumor Res., 1980, 15, 1–10.

    CAS  Google Scholar 

  34. P. J. Bugelski, C. W. Porter and T. J. Dougherty, Autoradiographic distribution of hematoporphyrin derivative in normal and tumor tissue of the mouse, Cancer Res., 1981, 41, 4606–4612.

    CAS  PubMed  Google Scholar 

  35. C. S. Loh, J. Bedwell, A. J. MacRobert, N. Krasner, D. Phillips and S. G. Bown, Photodynamic therapy of the normal rat stomach: a comparative study between di-sulphonated aluminium phthalocyanine and 5-aminolaevulinic acid, Br. J. Cancer, 1992, 66, 452–462.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. J. Leveckis, N. J. Brown and M. W. R. Reed, The effect of aminolaevulinic acid-induced protoporphyrin IX-mediated photodynamic therapy on the cremaster muscle microcirculation in vivo, Br. J. Cancer, 1995, 72, 1113–1119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. D. J. H. Roberts, F. Cairnduff, I. Driver, B. Dixon and S. B. Brown, Tumour vascular shutdown following photodynamic therapy based on polyhaematoporphyrin or 5-aminolaevulinic acid, Int. J. Oncol., 1994, 5, 763–768.

    CAS  PubMed  Google Scholar 

  38. N. van der Veen, H. L. van Leengoed and W. M. Star, In vivo fluorescence kinetics and photodynamic therapy using 5-aminolaevulinic acid-induced porphyrin: increased damage after multiple irradiations, Br. J. Cancer, 1994, 70, 867–872.

    Article  PubMed  PubMed Central  Google Scholar 

  39. H. Barr, C. J. Tralau, P. B. Boulos, A. J. MacRobert, R. Tilly and S. G. Bown, The contrasting mechanisms of colonic collagen damage between photodynamic therapy and thermal injury, Photochem. Photobiol., 1987, 46, 795–800.

    Article  CAS  PubMed  Google Scholar 

  40. G. I. Stables, M. R. Stringer, D. J. Robinson and D. V. Ash, Large patches of Bowen’s disease treated by topical aminolaevulinic acid photodynamic therapy, Br. J. Dermatol., 1997, 136, 957–960.

    Article  CAS  PubMed  Google Scholar 

  41. J. Regula, A. J. MacRobert, A. Gorchein, G. A. Buonaccorsi, S. M. Thorpe, G. M. Spencer, A. R. Hatfield and S. G. Bown, 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  CAS  PubMed  PubMed Central  Google Scholar 

  42. J. Webber, D. Kessel and D. Fromm, Side effects and photosensitization of human tissues after aminolevulinic acid, J. Surg. Res., 1997, 68, 31–37.

    Article  CAS  PubMed  Google Scholar 

  43. R Waidelich, H. Stepp, R. Baumgartner, E. Weninger, A. Hofstetter and M. Kriegmair, Clinical experience with 5-aminolevulinic acid and photodynamic therapy for refractory superficial bladder cancer, J. Urol., 2001, 165, 1904–1907.

    Article  CAS  PubMed  Google Scholar 

  44. A. J. MacRobert, M. D. Judd, J. Regula, C. S. Loh and S. G. Bown, Fluorescence studies of 5-aminolaevulinic acid induced protoporphyrin IX and sulphonates aluminimum phthalocyanine tissue distributions, SPIE J., 1993, 2081, 33–40.

    Google Scholar 

  45. I. J. Macdonald and T. J. Dougherty, Basic Principles of photodynamic therapy, J. Porphyrins Phthalocyanines, 2001, 5, 105–129.

    Article  CAS  Google Scholar 

  46. T. J. Dougherty, C. J. Gomer, B. W. Henderson, G. Jori, D. Kessel, M. Korbelik, J. Moan and Q. Peng, Photodynamic therapy, J. Natl. Cancer Inst., 1998, 90, 889–905.

    Article  CAS  PubMed  Google Scholar 

  47. J. J. Schuitmaker, P. Baas, H. L. van Leengoed, F. W. van der Meulen, W. M. Star and N. van Zandwijk, Photodynamic therapy: a promising new modality for the treatment of cancer, J. Photochem. Photobiol., B, 1996, 34, 3–12.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  49. B. B. Noodt, K. Berg, T. Stokke, Q. Peng and J. M. Nesland, Apoptosis and necrosis induced with light and 5-aminolaevulinic acid-derived protoporphyrin IX, Br. J. Cancer, 1996, 74, 22–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. X. Y. He, R. A. Sikes, S. Thomsen, L. W. Chung and S. L. Jacques, Photodynamic therapy with photofrin II induces programmed cell death in carcinoma cell lines, Photochem. Photobiol., 1994, 59, 468–473.

    Article  CAS  PubMed  Google Scholar 

  51. M. L. Agarwal, M. E. Clay, E. J. Harvey, H. H. Evans, A. R. Antunez and N. L. Oleinick, Photodynamic therapy induces rapid cell death by apoptosis in L5178Y mouse lymphoma cells, Cancer Res., 1991, 51, 5993–5996.

    CAS  PubMed  Google Scholar 

  52. C. N. Zhou, Mechanisms of tumour necrosis induced by photodynamic therapy, J. Photochem. Photobiol., B, 1989, 3, 299–318.

    Article  CAS  Google Scholar 

  53. M. Korbelik, Induction of tumor immunity by photodynamic therapy, J. Clin. Laser Med. Surg., 1996, 14, 329–334.

    Article  CAS  PubMed  Google Scholar 

  54. B. W. Henderson, S. M. Waldow, T. S. Mang, W. R. Potter, P. B. Malone and T. J. Dougherty, Tumor destruction and kinetics of tumor cell death in two experimental mouse tumors following photodynamic therapy, Cancer Res., 1985, 45, 572–576.

    CAS  PubMed  Google Scholar 

  55. M. W. Reed, F. N. Miller, T. J. Wieman, M. T. Tseng and C. G. Pietsch, The effect of photodynamic therapy on the microcirculation, J. Surg. Res., 1988, 45, 452–459.

    Article  CAS  PubMed  Google Scholar 

  56. V. H. Fingar, T. J. Wieman, S. A. Wiehle and P. B. Cerrito, The role of microvascular damage in photodynamic therapy: the effect of treatment on vessel constriction, permeability, and leukocyte adhesion, Cancer Res., 1992, 52, 4914–4921.

    CAS  PubMed  Google Scholar 

  57. J. C. Kennedy, R. H. Pottier and D. C. Pross, Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience, J. Photochem. Photobiol., B, 1990, 6, 143–148.

    Article  CAS  Google Scholar 

  58. F. Cairnduff, M. R. Stringer, E. J. Hudson, D. V. Ash and S. B. Brown, Superficial photodynamic therapy with topical 5-aminolaevulinic acid for superficial primary and secondary skin cancer, Br. J. Cancer, 1994, 69, 605–608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. D. Omrod and B. Jarvis, Topical aminolevulinic acid HCl photodynamic therapy, Am. J. Clin. Dermatol., 2000, 1, 133–139.

    Article  Google Scholar 

  60. C. A. Morton, C. Whitehurst, J. H. McColl, J. V. Moore and R. M. MacKie, Photodynamic therapy for large or multiple patches of Bowen disease and basal cell carcinoma, Arch. Dermatol., 2001, 137, 319–324.

    CAS  PubMed  Google Scholar 

  61. C. A. Morton, C. Whitehurst, J. V. Moore and R. M. MacKie, Comparison of red and green light in the treatment of Bowen’s disease by photodynamic therapy, Br. J. Dermatol., 2000, 143, 767–772.

    Article  CAS  PubMed  Google Scholar 

  62. I. Wang, B. Bauer, S. Andersson-Engels, S. Svanberg and K. Svanberg, Photodynamic therapy utilising topical delta-aminolevulinic acid in non-melanoma skin malignancies of the eyelid and the periocular skin, Acta Ophthalmol. Scand., 1999, 77, 182–188.

    Article  CAS  PubMed  Google Scholar 

  63. P. G. Calzavara-Pinton, Repetitive photodynamic therapy with topical delta-aminolaevulinic acid as an appropriate approach to the routine treatment of superficial non-melanoma skin tumours, J. Photochem. Photobiol., B, 1995, 29, 53–57.

    Article  CAS  Google Scholar 

  64. R. Fink-Puches, A. Hofer, J. Smolle, H. Kerl and P. Wolf, Primary clinical response and long-term follow-up of solar keratoses treated with topically applied 5-aminolevulinic acid and irradiation by different wave bands of light, J. Photochem. Photobiol., B, 1997, 41, 145–151.

    Article  CAS  Google Scholar 

  65. R. Fink-Puches, H. P. Soyer, A. Hofer, H. Kerl and P. Wolf, Long-term follow-up and histological changes of superficial nonmelanoma skin cancers treated with topical delta-aminolevulinic acid photodynamic therapy, Arch. Dermatol., 1998, 134, 821–826.

    Article  CAS  PubMed  Google Scholar 

  66. C. Fritsch, H. Stege, G. Saalmann, G. Goerz, T. Ruzicka and J. Krutmann, Green light is effective and less painful than red light in photodynamic therapy of facial solar keratoses, Photodermatol. Photoimmunol. Photomed., 1997, 13, 181–5.

    Article  CAS  PubMed  Google Scholar 

  67. A. M. Soler, T. Warloe, J. Tausjo and A. Berner, Photodynamic therapy by topical aminolevulinic acid, dimethylsulphoxide and curettage in nodular basal cell carcinoma: a one-year follow-up study, Acta Derm.-Venereol., 1999, 79, 204–206.

    Article  CAS  PubMed  Google Scholar 

  68. A. M. Soler, E. Angell-Petersen, T. Warloe, J. Tausjo, H. B. Steen, J. Moan and K. E. Giercksky, Photodynamic therapy of superficial basal cell carcinoma with 5-aminolevulinic acid with dimethylsulfoxide and ethylenediaminetetraacetic acid: a comparison of two light sources, Photochem. Photobiol., 2000, 71, 724–729.

    Article  CAS  PubMed  Google Scholar 

  69. R. Ammann, T. Hunziker and L. R. Braathen, Topical photodynamic therapy in verrucae. A pilot study, Dermatology, 1995, 191, 346–347.

    Article  CAS  PubMed  Google Scholar 

  70. I. M. Stender, J. Lock-Andersen and H. C. Wulf, Recalcitrant hand and foot warts successfully treated with photodynamic therapy with topical 5-aminolaevulinic acid: a pilot study, Clin. Exp. Dermatol., 1999, 24, 154–159.

    Article  CAS  PubMed  Google Scholar 

  71. I. M. Stender, R. Na, H. Fogh, C. Gluud and H. C. Wulf, Photodynamic therapy with 5-aminolaevulinic acid or placebo for recalcitrant foot and hand warts: randomised double-blind trial, Lancet, 2000, 355, 963–966.

    Article  CAS  PubMed  Google Scholar 

  72. Y. Itoh, Y. Ninomiya, T. Henta, S. Tajima and A. Ishibashi, Topical delta-aminolevulinic acid-based photodynamic therapy for Japanese actinic keratoses, J. Dermatol., 2000, 27, 513–518.

    Article  CAS  PubMed  Google Scholar 

  73. D. J. Robinson, P. Collins, M. R. Stringer, D. I. Vernon, G. I. Stables, S. B. Brown and R. A. Sheehan-Dare, Improved response of plaque psoriasis after multiple treatments with topical 5-aminolaevulinic acid photodynamic therapy, Acta Derm.-Venereol., 1999, 79, 451–455.

    Article  CAS  PubMed  Google Scholar 

  74. W. Hongcharu, C. R. Taylor, Y. Chang, D. Aghassi, K. Suthamjariya and R. R. Anderson, Topical ALA-photodynamic therapy for the treatment of acne vulgaris, J. Invest. Dermatol., 2000, 115, 183–192.

    Article  CAS  PubMed  Google Scholar 

  75. G. I. Stables, M. R. Stringer, D. J. Robinson and D. V. Ash, Erythroplasia of Queyrat treated by topical aminolaevulinic acid photodynamic therapy, Br. J. Dermatol., 1999, 140, 514–517.

    Article  CAS  PubMed  Google Scholar 

  76. P. Wolf, R. Fink-Puches, A. Reimann-Weber and H. Kerl, Development of malignant melanoma after repeated topical photodynamic therapy with 5-aminolevulinic acid at the exposed site, Dermatology, 1997, 194, 53–54.

    Article  CAS  PubMed  Google Scholar 

  77. W. C. Tan, C. Fulljames, N. Stone, A. J. Dix, N. Shepherd, D. J. Roberts, S. B. Brown, N. Krasner and H. Barr, Photodynamic therapy using 5-aminolaevulinic acid for oesophageal adenocarcinoma associated with Barrett’s metaplasia, J. Photochem. Photobiol., B, 1999, 53, 75–80.

    Article  CAS  Google Scholar 

  78. L. Gossner, M. Stolte, R. Sroka, K. Rick, A. May, E. G. Hahn and C. Ell, Photodynamic ablation of high-grade dysplasia and early cancer in Barrett’s esophagus by means of 5-aminolevulinic acid, Gastroenterology, 1998, 114, 448–455.

    Article  CAS  PubMed  Google Scholar 

  79. R. Ackroyd, N. J. Brown, M. F. Davis, T. J. Stephenson, S. L. Marcus, C. J. Stoddard, A. G. Johnson and M. W. R. Reed, Photodynamic therapy for dysplastic Barrett’s oesophagus: a prospective, double blind, randomised, placebo controlled trial, Gut, 2000, 47, 612–617.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. C. J. Kelty, R. Ackroyd, N. J. Brown, T. J. Stephenson, C. J. Stoddard and M. W. R. Reed, Photodynamic therapy for dysplastic Barrett’s oesophagus: Long-term follow-up, Br. J. Surg., 2001, 88, 478.

    Article  Google Scholar 

  81. M. A. Ortner, K. Zumbusch, J. Liebetruth, H. Ernst, J. Weber, J. Wirth, S. Wedel and H. Lochs, Photodynamic therapy of Barrett’s esophagus after local administration of 5-aminolevulinic acid, Gastroenterology, 1997, 112, A633.

    Google Scholar 

  82. H. Kashtan, F. Konikoff, R. Haddad, M. Umansky, Y. Skornick and Z. Halpern, [Photodynamic therapy for dysphagia due to esophageal carcinoma], Harefuah, 1999, 137, 441–444, 512.

    CAS  PubMed  Google Scholar 

  83. T. Zoepf, R. Jakobs, A. Rosenbaum, D. Apel, J. C. Arnold and J. F. Riemann, Photodynamic Therapy with 5-Aminolevulinic acid is not effective in Bile duct cancer, Gastroenterology, 1999, 118, A528.

    Article  Google Scholar 

  84. M. Kriegmair, R. Baumgartner, W. Lumper, R. Waidelich and A. Hofstetter, Early clinical experience with 5-aminolevulinic acid for the photodynamic therapy of superficial bladder cancer, Br. J. Urol., 1996, 77, 667–671.

    Article  CAS  PubMed  Google Scholar 

  85. R. Waidelich, A. Hofstetter, H. Stepp, R. Baumgartner, E. Weninger and M. Kriegmair, Early clinical experience with 5-aminolevulinic acid for the photodynamic therapy of upper tract urothelial tumors, J. Urol., 1998, 159, 401–404.

    Article  CAS  PubMed  Google Scholar 

  86. M. P. Jenkins, G. A. Buonaccorsi, M. Raphael, I. Nyamekye, J. R. McEwan, S. G. Bown and C. C. Bishop, Clinical study of adjuvant photodynamic therapy to reduce restenosis following femoral angioplasty, Br. J. Surg., 1999, 86, 1258–1263.

    Article  CAS  PubMed  Google Scholar 

  87. K. F. Fan, C. Hopper, P. M. Speight, G. Buonaccorsi, A. J. MacRobert and S. G. Bown, Photodynamic therapy using 5-aminolevulinic acid for premalignant and malignant lesions of the oral cavity, Cancer, 1996, 78, 1374–1383.

    Article  CAS  PubMed  Google Scholar 

  88. A. Kubler, T. Haase, M. Rheinwald, T. Barth and J. Muhling, Treatment of oral leukoplakia by topical application of 5-aminolevulinic acid, Int. J. Oral Max. Surg., 1998, 27, 466–469.

    Article  CAS  Google Scholar 

  89. P. Hillemanns, M. Korell, M. Schmitt-Sody, R. Baumgartner, W. Beyer, R. Kimmig, M. Untch and H. Hepp, Photodynamic therapy in women with cervical intraepithelial neoplasia using topically applied 5-aminolevulinic acid, Int. J. Cancer, 1999, 81, 34–38.

    Article  CAS  PubMed  Google Scholar 

  90. P. Hillemanns, M. Untch, C. Dannecker, R. Baumgartner, H. Stepp, J. Diebold, H. Weingandt, F. Prove and M. Korell, Photodynamic therapy of vulvar intraepithelial neoplasia using 5-aminolevulinic acid, Int. J. Cancer, 2000, 85, 649–653.

    Article  CAS  PubMed  Google Scholar 

  91. P. Hillemanns, M. Untch, F. Prove, R. Baumgartner, M. Hillemanns and M. Korell, Photodynamic therapy of vulvar lichen sclerosus with 5-aminolevulinic acid, Obstet. Gynecol., 1999, 93, 71–74.

    CAS  PubMed  Google Scholar 

  92. S. N. Datta, C. S. Loh, A. J. MacRobert, S. D. Whatley and P. N. Matthews, Quantitative studies of the kinetics of 5-aminolaevulinic acid-induced fluorescence in bladder transitional cell carcinoma, Br. J. Cancer, 1998, 78, 1113–1118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. M. Kriegmair, R. Baumgartner, R. Knuechel, P. Steinbach, A. Ehsan, W. Lumper, F. Hofstadter and A. Hofstetter, Fluorescence photodetection of neoplastic urothelial lesions following intravesical instillation of 5-aminolevulinic acid, Urology, 1994, 44, 836–841.

    Article  CAS  PubMed  Google Scholar 

  94. M. Kriegmair, R. Baumgartner, R. Knuchel, A. Ehsan, P. Steinbach, W. Lumper, F. Hofstadter and A. Hofstetter, [Photodynamic diagnosis of urothelial neoplasms after intravesicular instillation of 5-aminolevulinic acid], Urologe A, 1994, 33, 270–275.

    CAS  PubMed  Google Scholar 

  95. M. Kriegmair, D. Zaak, H. Stepp, R. Baumgartner, R. Knuechel and A. Hofstetter, Transurethral resection and surveillance of bladder cancer supported by 5-aminolevulinic acid-induced fluorescence endoscopy, Eur. Urol., 1999, 36, 386–392.

    Article  CAS  PubMed  Google Scholar 

  96. P. Jichlinski, G. Wagnieres, M. Forrer, J. Mizeret, L. Guillou, M. Oswald, F. Schmidlin, P. Graber, H. Van den Bergh and H. J. Leisinger, Clinical assessment of fluorescence cytoscopy during transurethral bladder resection in superficial bladder cancer, Urol. Res., 1997, 25, S3–6.

    Article  PubMed  Google Scholar 

  97. F. Koenig, F. J. McGovern, R. Larne, H. Enquist, K. T. Schomacker and T. F. Deutsch, Diagnosis of bladder carcinoma using protoporphyrin IX fluorescence induced by 5-aminolaevulinic acid, Br. J. Urol., 1999, 83, 129–135.

    Article  CAS  Google Scholar 

  98. T. Filbeck, W. Roessler, R. Knuechel, M. Straub, H. J. Kiel and W. F. Wieland, 5-aminolevulinic acid-induced fluorescence endoscopy applied at secondary transurethral resection after conventional resection of primary superficial bladder tumors, Urology, 1999, 53, 77–81.

    Article  CAS  PubMed  Google Scholar 

  99. T. Filbeck, M. B. Wimmershoff, U. Pichlmeier, S. Karrer, W. F. Wieland, R. M. Szeimies and W. Rossler, No generalized skin phototoxicity after intravesical application of 5-aminolevulinic acid for fluorescence diagnosis of superficial bladder cancer, Urol. Int., 2000, 64, 126–128.

    Article  CAS  PubMed  Google Scholar 

  100. P. Hillemanns, H. Weingandt, H. Stepp, R. Baumgartner, W. Xiang and M. Korell, Assessment of 5-aminolevulinic acid-induced porphyrin fluorescence in patients with peritoneal endometriosis, Am. J. Obstet. Gynecol., 2000, 183, 52–57.

    CAS  PubMed  Google Scholar 

  101. P. Hillemanns, H. Weingandt, R. Baumgartner, J. Diebold, W. Xiang and H. Stepp, Photodetection of cervical intraepithelial neoplasia using 5-aminolevulinic acid-induced porphyrin fluorescence, Cancer, 2000, 88, 2275–2282.

    Article  CAS  PubMed  Google Scholar 

  102. R. Baumgartner, R. M. Huber, H. Schulz, H. Stepp, K. Rick, F. Gamarra, A. Leberig and C. Roth, Inhalation of 5-aminolevulinic acid: a new technique for fluorescence detection of early stage lung cancer, J. Photochem. Photobiol., B, 1996, 36, 169–174.

    Article  CAS  Google Scholar 

  103. D. P. Ladner, R. A. Steiner, J. Allemann, U. Haller and H. Walt, Photodynamic diagnosis of breast tumours after oral application of aminolevulinic acid, Br. J. Cancer, 2001, 84, 33–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. M. Novo, G. Huttmann and H. Diddens, Chemical instability of 5-aminolevulinic acid used in the fluorescence diagnosis of bladder tumours, J. Photochem. Photobiol., B, 1996, 34, 143–148.

    Article  CAS  Google Scholar 

  105. J. Kloek, W. Akkermans and G. M. Beijersbergen van Henegouwen, Derivatives of 5-aminolevulinic acid for photodynamic therapy: enzymatic conversion into protoporphyrin, Photochem. Photobiol., 1998, 67, 150–154.

    Article  CAS  PubMed  Google Scholar 

  106. Q. Peng, J. Moan, T. Warloe, V. Iani, H. B. Steen, A. Bjorseth and J. M. Nesland, Build-up of esterified aminolevulinic-acid-derivative-induced porphyrin fluorescence in normal mouse skin, J. Photochem. Photobiol., B, 1996, 34, 95–96.

    Article  CAS  Google Scholar 

  107. N. Lange, P. Jichlinski, M. Zellweger, M. Forrer, A. Marti, L. Guillou, P. Kucera, G. Wagnieres and H. van den Bergh, Photodetection of early human bladder cancer based on the fluorescence of 5-aminolaevulinic acid hexylester-induced protoporphyrin IX: a pilot study, Br. J. Cancer, 1999, 80, 185–193.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. A. Curnow, J. C. Haller and S. G. Bown, Oxygen monitoring during 5-aminolaevulinic acid induced photodynamic therapy in normal rat colon. Comparison of continuous and fractionated light regimes, J. Photochem. Photobiol., B, 2000, 58, 149–155.

    Article  CAS  Google Scholar 

  109. A. Curnow, B. W. McIlroy, M. J. Postle-Hacon, A. J. MacRobert and S. G. Bown, Light dose fractionation to enhance photodynamic therapy using 5-aminolevulinic acid in the normal rat colon, Photochem. Photobiol., 1999, 69, 71–76.

    Article  CAS  PubMed  Google Scholar 

  110. C. Whitehurst, K. Byrne and J. V. Moore, Development of an alternative light source to lasers for photodynamic therapy: 1. Comparative in vitro dose response characteristics, Lasers Med. Sci., 1993, 49, 760–764.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Academic Surgical Oncology Unit, Section of Clinical Sciences, University of Sheffield, Glossop Road, Sheffield, UK, S10 2JF

    Clive J. Kelty, Nicola J. Brown & Malcolm W. R. Reed

  2. Department of Surgery, Royal Hallamshire Hospital, Glossop Road, Sheffield, UK, S10 2JF

    Roger Ackroyd

Authors
  1. Clive J. Kelty
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicola J. Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Malcolm W. R. Reed
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Roger Ackroyd
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Clive J. Kelty is Clinical Research Fellow in the Academic Unit of Surgical Oncology at the University of Sheffield. He qualified in Medicine from the University of Glasgow, and trained in surgery in Leeds, Sheffield and Newcastle, UK. Since 2000, he has been working towards an MD in the endoscopic ablation of Barrett’s oesophagus, comparing photodynamic therapy and argon plasma coagulation.

Nicola J. Brown is Reader in Surgical Sciences, in the Academic Unit of Surgery, University of Sheffield, and Director of the Microcirculation Research Unit. She received her PhD in Physiology in 1987, from the University of Sheffield. In recent years, since establishing the Microcirculation Research Unit with Professor Malcolm Read in 1991, her research expertise has focussed on mechanisms of angiogenesis, and the role of the tumour microcirculation in cancer therapy, including photodynamic therapy. She is visiting Professor to the laboratory of Professor Peter Vaupel, Institute for Physiology and Pathophysiology, University of Mainz, Germany where she studies hypoxia induced by photodynamic therapy. Dr Brown’s specific areas of interest are understanding the mechanisms of both vascular and stress responses to photodynamic therapy, and the treatment of Barrett’s oesophagus.

Malcolm W. R. Reed was born and educated in Birmingham and undertook medical undergraduate training at the University of Sheffield. As an undergraduate student he undertook a BMedSci with Professor James Underwood looking at hormone receptors in breast cancer. Postgraduate training was undertaken in Bristol, Birmingham and Sheffield. He spent 18 months as a research fellow in the Department of Physiology in the University of Louisville, Kentucky, USA, studying the effect of photodynamic therapy on the tumour microcirculation. This resulted in a long-term interest in PDT and the microcirculation, which continues to be at the centre of the research of the Surgical Oncology unit. The unit is actively researching the role of PDT in the treatment of Barrett’s oesophagus and oesophageal cancer alongside basic science studies focussing on the vascular effects of PDT in vitro and in vivo. In 1992, Professor Reed was appointed Senior Lecturer at the University of Sheffield and subsequently Consultant Surgeon, Central Sheffield University Hospitals in 1996. He took up the foundation Chair in Surgical Oncology in August 1999.

Roger Ackroyd is Consultant Upper Gastrointestinal Surgeon at the Royal Hallamshire Hospital, Sheffield, UK. He qualified in Medicine from Sheffield University, and trained in surgery in Sheffield, England and Adelaide, Australia. His clinical interests include oesophago-gastric cancer, laparoscopic anti-reflux surgery, and morbid obesity. He obtained his MD with distinction on the use of photodynamic therapy in dysplastic Barrett’s oesophagus, and his research interests include photodynamic therapy, and ablative therapies for Barrett’s oesophagus.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kelty, C.J., Brown, N.J., Reed, M.W.R. et al. The use of 5-aminolaevulinic acid as a photosensitiser in photodynamic therapy and photodiagnosis. Photochem Photobiol Sci 1, 158–168 (2002). https://doi.org/10.1039/b201027p

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1039/b201027p

Search

Navigation