Pharmaceutical Research

, Volume 17, Issue 12, pp 1447–1455 | Cite as

Photodynamic Therapy of Skin Cancers: Sensitizers, Clinical Studies and Future Directives

  • Fernanda S. De Rosa
  • M. Vitória L. B. Bentley


Photodynamic therapy (PDT) is a new modality of skin cancer treatment. It involves the administration of photosensitizing drugs which, when localized in tumor tissue can produce its destruction by absorbing an adequate dose of light of an appropriate wavelength. A large number of photosensitizing agents have been tested in PDT experiments. Topical application of 5-aminolevulinic acid (5-ALA) followed by light irradiation is the most commonly used method. 5-ALA is a prodrug converted in situ via the heme cycle into protoporphyrin IX, an effective photosensitizer agent. Treatment of nonmelanoma skin cancers by PDT has met with varying degrees of success. In the case of 5-ALA, this therapy's main limitation is the poor penetration of 5-ALA into skin, due to hydrophilic and charge characteristics. However, the efficacy of 5-ALA-PDT may be improved by (a) development of adequate drug delivery systems; (b) use of enhancers of PpIX production and accumulation in target tissue, and (c) modifications of the 5-ALA molecule. Optimal timing, light sources, doses, and number of applications are also important factors for topical 5-ALA therapy and must be well defined. The aim of this review is to highlight recent progress in 5-ALA-PDT of skin cancer, and to present ways holding promise for its improvement.

photodynamic therapy 5-aminolevulinic acid photosensitizer protoporphyrin IX skin cancer 


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  1. 1.
    H. I. Pass. Photodynamic therapy in oncology: mechanisms and clinical use. J. Natl. Cancer Inst. 85:443–456 (1993).Google Scholar
  2. 2.
    T. J. Dougherty, J. E. Kaufman, A. Goldfarb, K. H. Weishaupt, D. Boyle, and A. Mittleman. Photoradiation therapy for the treatment of malignant tumors. Cancer Res. 38:2628–2635 (1978).Google Scholar
  3. 3.
    D. J. Roberts and F. Cairnduff. Photodynamic therapy of primary skin cancer: a review. Br. J. Plast. Surgery. 48:369–370 (1995).Google Scholar
  4. 4.
    S. L. Gibson, J. J. Havens, M. L. Nguyen, and R. Hilf. δ-Aminolevulinic acid-induced photodynamic therapy inhibits protoporphyrin IX biosynthesis and reduces subsequent treatment efficacy in vitro. Br. J. Cancer 80:998–1004 (1999).Google Scholar
  5. 5.
    M. T. Bastiaens, J. J. Hoefnagel, J. Á. Bruijn, R. G. J. Westendorp, B. J. Vermeer, and J. N. B. Bavinck. Differences in age, site distribution, and sex between nodular and superficial basal cell carcinomas indicate different types of tumors. J. Invest. Dermatol. 110:80–884 (1998).Google Scholar
  6. 6.
    Q. Peng, T. Warloe, J. Moan, H. Heyerdahl, H. B. Steen, J. M. Nesland, and K. E. Giercksky. Distribution of 5-aminolevulinic acid-induced porphyrins in noduloucerative basal cell carcinoma. Photochem. Photobiol. 62:906–913 (1995).Google Scholar
  7. 7.
    I. M. Stender and H. C. Wulf. Photodynamic therapy with 5-aminolevulinic acid in the treatment of actinic cheilitis. Br. J. Dermatol. 135:454–456 (1996).Google Scholar
  8. 8.
    R. M. Szeimies and S. A. Karrer. Photodynamic therapy with topical application of 5-aminolevulinic acid in the treatment of actinic keratoses: an initial clinical study. Dermatology 192:246–251 (1996).Google Scholar
  9. 9.
    A. M. Wennberg, L. E. Lindholm, M. Alpsten, and O. Larkö. Treatment of superficial basal cell carcinomas using topically applied delta-aminolevulinic acid and a filtered xenon lamp. Arch. Dermatol. Res. 288:561–564 (1996).Google Scholar
  10. 10.
    B. Ortel, P. G. Calzavara-Pinton, R. M. Szeimies, and T. Hasan. Perspectives in cutaneous photodynamic sensitization. J. Photochem. Photobiol. B 36:209–211 (1996).Google Scholar
  11. 11.
    K. Kalka, H. Merk, and H. Mukhtar. Photodynamic therapy in dermatology. J. Am. Acad. Dermatol. 42:389–413 (2000).Google Scholar
  12. 12.
    C. Fritsch, G. Goerz, and T. Ruzicka. Photodynamic therapy in dermatology. Arch. Dermatol. 134:207–214 (1998).Google Scholar
  13. 13.
    T. J. Dougherty. Photoradiation therapy for cutaneous and subcutaneous malignancies. J. Invest. Dermatol. 77:122–124 (1981).Google Scholar
  14. 14.
    O. Santoro, G. Bandieramonte, E. Melloni, R. Marchesini, F. Zunino, P. Lepera, and G. De Palo. Photodynamic therapy by topical mete-tetraphenylporphinesulphonate tetrasodium salt administration in superficial basal cell carcinomas. Cancer Res. 50: 4501–4503 (1990).Google Scholar
  15. 15.
    T. A. Katsumi, K. Aizawa, Y. Kuroiwa, K. Saito, Y. Kurata, Y. Ii, T. Okunaka, C. Konaka, and H. Kato: Photodynamic therapy with a diode laser for implanted fibrosarcoma in mice employing mono-L-aspartyl chlorin E6. Photochem. Photobiol. 64:671–675 (1996).Google Scholar
  16. 16.
    J. D. Spikes. New trends in photobiology: chlorins as photosensitizers in biology and medicine. J. Photochem. Photobiol. B 6: 259–274 (1990).Google Scholar
  17. 17.
    G. Canti, P. Franco, O. Marelli, R. Cubeddu, P. Taroni, and R. Ramponi. Comparative study of the therapeutic effect of photoactivated hematoporphyrin derivative and aluminum disulfonated phthalocyanines on tumor bearing mice. Cancer Lett. 53: 123–127 (1990).Google Scholar
  18. 18.
    C. Abels, R.-M. Szeimiesc, P. Steinbachd, C. Richerta, and A. E. Goetzb. Targeting of the tumor microcirculation by photodynamic therapy with a synthetic porphycene. J. Photochem. Photobiol. B 40:305–312 (1997).Google Scholar
  19. 19.
    M. Alecu, C. Ursaciuc, F. Halalau, G. Coman, W. Merlevede, E. Waelkens, and P. De Witte. Photodynamic treatment of basal cell carcinoma and SCC with hypericin. Anticancer Res. 18:4651–4654 (1998).Google Scholar
  20. 20.
    C. M. Schempp, B. Simon-Haarhaus, A. Heine, E. Schopf, and J. C. Simon. In vitro and in vivo activation of hypericin with the incoherent light source PDT 1200 SOA (520–750 nm) and with solar simulated radiation (290–2500 nm). Photodermatol. Photoimmunol. Photomed. 15:13–17 (1999).Google Scholar
  21. 21.
    G. Kostenich, A. Orenstein, L. Roitman, Z. Malik, and B. Ehrenberg. In vivo photodynamic therapy with the new near-IR absorbing water soluble photosensitizer lutetium texaphyrin and a high intensity pulsed light delivery system. J. Photochem. Photobiol. B 39:36–42 (1997).Google Scholar
  22. 22.
    G. G. Miller, K. Brown, R. B. Moore, Z. J. Diwu, J. Liu, L. Huang, J. W. Lown, D. A. Begg, V. Chlumecky, and J. Tulip. Uptake kinetics and intracellular localization of hypocrellin photosensitizers for photodynamic therapy: a confocal microscopy study. Photochem. Photobiol. 61:632–638 (1995).Google Scholar
  23. 23.
    G. J. Fowler, R.C. Rees, and R. Devonshire. The photokilling of bladder carcinoma cells in vitro by phenothiazine dyes. Photochem. Photobiol. 52:489–494 (1990).Google Scholar
  24. 24.
    D. J. Castro, R. E. Saxton, H. R. Fetterman, D. J. Castro, and P. H. Ward. Rhodamine-123 as a new chemosensitizing versus toxic agent on human squamous carcinoma cells and fibroblast cultures. J. Clin. Laser Med. Surg. 10:83–90 (1992).Google Scholar
  25. 25.
    P. Wolf, E. Rieger, and H. Kerl. Topical photodynamic therapy with endogenous porphyrins after application of 5-aminolevulinic acid. J. Am. Acad. Dermatol. 28:17–21 (1993).Google Scholar
  26. 26.
    F. Cairnduff, M. R. Stringer, E. J. Hudson, D.V. Ash, and S. B. Brown. Superficial photodynamic therapy with topical 5-aminolevulinic acid for superficial primary and secondary skin cancer. Br. J. Cancer 69:605–608 (1994).Google Scholar
  27. 27.
    Q. Peng, J. Moan, and J. M. Nesland. Correlation of subcellular and intratumoral photosensitizer localization with ultrastructural features after photodynamic therapy. Ultrastruc. Pathol. 20:109–129 (1996).Google Scholar
  28. 28.
    J. C. Kennedy and R. H. Pottier. Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy. J. Photochem. Photobiol. B 14:275–292 (1992).Google Scholar
  29. 29.
    C. Fritsch, B. Verwohlt, K. Bolsen, T. Ruzicka, and G. Goerz: Influence of topical photodynamic therapy with 5-aminolevulinic acid on porphyrin metabolism. Arch. Dermatol. Res. 288:517–521 (1996).Google Scholar
  30. 30.
    D. Kessel and Y. Luo. Mitochondrial photodamage and PDTinduced apoptosis. J. Photochem. Photobiol. B 42:89–95 (1998).Google Scholar
  31. 31.
    B. W. Henderson, and T. J. Dougherty. How does photodynamic therapy work? Photochem. Photobiol. 55:145–157 (1992).Google Scholar
  32. 32.
    R. M. Szeimies, P. G. Calzavara-Pinton, S. Karrer, B. Ortel, and M. Landthaler. Topical photodynamic therapy in dermatology. J. Photochem. Photobiol. B 36:213–219 (1996).Google Scholar
  33. 33.
    P. G. Calzavara-Pinton. Repetitive photodynamic therapy with topical δ-aminolevulinic acid as an appropriate approach to the routine treatment of superficial non-melanoma skin tumours. J. Photochem. Photobiol. B 29:53–57 (1995).Google Scholar
  34. 34.
    B. A. Goff, R. Bachor, N. Kollias, and T. Hasan. Effects of photodynamic therapy with topical application of 5-aminolevulinic acid on normal skin of hairless guinea pigs. J. Photochem. Photobiol. B 15:239–251 (1992).Google Scholar
  35. 35.
    R. M. Szeimies, R. Hein, W. Baümler, A. Heine, and M. Landthaler. A possible new incoherent lamp for photodynamic treatment of superficial skin lesions. Acta Dermatol. Venereol. 59:73–76 (1994).Google Scholar
  36. 36.
    R. M. Szeimies, C. Abels, C. Fritsch, S. Karrer, P. Steinbach, W. Baumler, G. Goerz, A. E. Goetz, and M. Landthaler. Wavelength dependency of photodynamic effects after sensitization with 5-aminolevulinic acid in vitro and in vivo. J. Invest. Dermatol. 105:672–677 (1995).Google Scholar
  37. 37.
    P. Charlesworth and T. G. Truscott. The use of 5-aminolevulinic acid (ALA) in photodynamic therapy. J. Photochem. Photobiol. B 18:99–100 (1993).Google Scholar
  38. 38.
    W. M. Star. Light dosimetry in vivo. Phys. Med. Biol. 42:763–787 (1997).Google Scholar
  39. 39.
    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 6:143–148 (1990).Google Scholar
  40. 40.
    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-aminolevulinic acid correlates with localized protoporphyrin IX fluorescence. Am. J. Pathol. 136:891–897 (1990).Google Scholar
  41. 41.
    P. Wolf and H. Kerl. Photodynamic therapy with 5-aminolevulinic acid: a promising concept for the treatment of cutaneous tumors. Dermatology 190:183–185 (1995).Google Scholar
  42. 42.
    C. Abels, P. Heil, M. Dellian, G. E. H. Kuhnle, R. Baumgartner, and A. E. Goetz. In vivo kinetics and spectra of 5-aminolevulinic acid-induced fluorescence in an amelanotic melanoma of the hamster. Br. J. Cancer 70:826–833 (1994).Google Scholar
  43. 43.
    M. Kriegmeir, R. Baumgartner, R. Kneuchel, H. Stepp, F. Hofsteder, and A. Hofstetter. Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence. J. Urol. 155:105–110 (1996).Google Scholar
  44. 44.
    Ø. Bech, K. Berg, and J. Moan. The pH dependency of protoporphyrin IX formation in cells incubated with 5-aminolevulinic acid. Cancer Lett. 113:25–29 (1997).Google Scholar
  45. 45.
    S. L. Gibson, D. J. Cupriks, J. J. Havens, M. L. Nguyen, and R. Hilf. A regulatory role for porphobilinogen deaminase (PBGD) in δ-aminolevulinic acid (d-5-ALA)-induced photosensitization? Br. J. Cancer 77:235–243 (1998).Google Scholar
  46. 46.
    O. Trepte, I. Rokahr, S. Anderson-Engels, and K. Carlsson. Studies of porphyrin-containing specimens using an optical spectrometer connected to a confocal scanning laser microscope. J. Microscopy 176:238–244 (1994).Google Scholar
  47. 47.
    S. Iinuma, S. S. Farshi, B. Ortel, and T. Hasan. A mechanistic study of cellular photodestruction with 5-aminolevulinic acidinduced porphyrin. Br. J. Cancer 70:21–28 (1994).Google Scholar
  48. 48.
    K. Tabata, S. Ogura, and I. Okura. Photodynamic efficiency of protoporphyrin IX: comparison of endogenous protoporphyrin IX induced by 5-aminolevulinic acid and exogenous porphyrin IX. Photochem. Photobiol. 66:842–846 (1997).Google Scholar
  49. 49.
    B. C. Wilson and G. Sngh. Subcellular localization of Photfrin and aminolevulinic acid and photodynamic cross-resistance in vitro in radiation-induced fibrosarcoma cells sensitive or resistant to Photofrin-mediated photodynamic therapy. Photochem. Photobiol. 65:166–176 (1997).Google Scholar
  50. 50.
    J. J. Schuitmaker, P. Baas, H. L. L. M. 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 34:3–12 (1996).Google Scholar
  51. 51.
    K. Svanberg, T. Anderson, D. Killander, I. Wang, U. Stenram, S. Andersson-Engels, R. Berg, J. Johansson, and S. Svanberg. Photodynamic therapy of non-melanoma malignant tumours of the skin using topical δ-aminolevulinic acid sensitization and laser irradiation. Br. J. Dermatol. 130:743–751 (1994).Google Scholar
  52. 52.
    C. A. Morton, C. Whitehurst, H. Moseley, J. H. Mccoll, J. V. Moore, and R. Mackie. Comparison of photodynamic therapy with cryotherapy in the treatment of Bowen's disease. Br. J. Dermatol. 135:766–771 (1996).Google Scholar
  53. 53.
    E. W. Jeffes, J. L. Mccullough, G. D. Weinstein, P. E. Fergin, J. S. Nelson, T. F. Shull, K. R. Simpson, L. M. Bukaty, W. L. Hoffman, and N. L. Fong. Photodynamic therapy of actinic keratosis with topical 5-aminolevulinic acid. Arch. Dermatol. 133:727–732 (1997).Google Scholar
  54. 54.
    A. F. Hürlimann, G. Hänggi, and R. G. Panizzon. Photodynamic therapy of superficial basal cell carcinomas using topical aminolevulinic acid in a nanocolloid lotion. Dermatology 197:248–254 (1998).Google Scholar
  55. 55.
    C. Fritsch, C. Abels, A. E. Goetz, W. Stahl, K. Bolsen, T. Ruzicka, G. Goerz, and H. Sies. Porphyrins preferentially accumulate in a melanoma following intravenous injaction of 5-aminolevulinic acid. Biol. Chem. 378:51–57 (1997).Google Scholar
  56. 56.
    M. R. Stringer, P. Collins, D. J. Robinson, G. I. Stables, and R. A. Sheehan-Dare. The accumulation of protoporphyrin IX in plaque psoriasis after topical application of 5-aminolevulinic acid indicates a potential for superficial photodynamic therapy. J. Invest. Dermatol. 107:76–81 (1996).Google Scholar
  57. 57.
    G. I. Stables, M. R. Stringer, D. J. Robinson, and D. V. Ash. Large patches of Bowen's disease treated by topical aminolevulinic acid photodynamic therapy. Br. J. Dermatol. 136:957–960 (1997).Google Scholar
  58. 58.
    P. Ziolkowski, K. Symonowicz, P. Chmielewski, L. Latos-Grazynski, G. Streckyte, R. Rotomskis, and J. Rabczynski. New potent sensitizers for photodynamic therapy: 21-oxaporphyrin, 21-thiaporphyrin and 21,23-dithiaporphyrin induce extensive tumor necrosis. J. Cancer Res. Clin. Oncol. 125:563–568 (1999).Google Scholar
  59. 59.
    E. Reddi. Role of delivery vehicles for photosensitizers in the photodynamic therapy of tumours. J. Photochem. Photobiol. B 37:189–195 (1997).Google Scholar
  60. 60.
    Z. J. Wang, Y. Y. He, C. G. Huang, J. S. Huang, Y. C. Huang, J. Y. An. Y. Gu, and L. J. Jiang. Pharmacokinetics, tissue distribution and photodynamic therapy efficacy of liposomal-delivered hypocrellin A, a potential photosensitizer for tumor therapy. Photochem. Photobiol. 70:773–780 (1999).Google Scholar
  61. 61.
    J. Kloek, W. Akkermans, and G. M. J. B. Van Henegouwen. Derivatives of 5-aminolevulinic acid for Photodynamic Therapy: enzymatic conversion into protoporphyrin. Photochem. Photobiol. 67:150–154 (1998).Google Scholar
  62. 62.
    A. C. William and B. W. Barry. Skin absorption enhancers. Crit. Ver. Ther. Drug Carrier Syst. 9:305–353 (1992).Google Scholar
  63. 63.
    M. V. L. B. Bentley, R. F. Vianna, S. Wilson, and J. H. Collett. A characterisation of the influence of some cyclodextrins on the stratum corneum from the hairless mouse. J. Pharm. Pharmacol. 49:397–402 (1997).Google Scholar
  64. 64.
    N. Schoenfeld, R. Mamet, Y. Nordenberg, M. Shafran, T. Babushkin, and Z. Malik. Protoporphyrin biosynthesis in melanoma B16 cells stimulated by 5-aminolevulinic acid and chemical inducers: characterization of photodynamic inactivation. Int. J. Cancer 56:106–112 (1994).Google Scholar
  65. 65.
    H. Fujita, M. Yamamoto, T. Yamagami, N. Hayashi, T.R. Bishop, H. De Verneuil, T. Yoshinaga, S. Shibahara, R. Morimoto, and S. Sassa. Sequential activation of genes for heme pathway enzymes during erythroid differentiation of mouse Friend virus-transformed erythroleukemia cells. Biochem. Biophys. Acta 1090: 311–316 (1991).Google Scholar
  66. 66.
    A. N. C. Anigbogu, A. C. Williams, B. W. Barry, and H. G. M. Edwards. Fourier transform Raman spectroscopy of interactions between the penetration enhancer dimethylsulfoxide and human stratum corneum. Int. J. Pharm. 125:265–282 (1995).Google Scholar
  67. 67.
    J. Hanania and Z. Malik. The effect of EDTA and serum on endogenous-porphyrin accumulation and photodynamic sensitization of human K562 leukemic cells. Cancer Lett. 65:127–131 (1992).Google Scholar
  68. 68.
    F. S. De Rosa, J. M. Marchetti, J. A. Thomazini, A. C. Tedesco, and M. V. L. B. Bentley. A vehicle for photodynamic therapy of skin cancer:influence of dimethylsulphoxide on 5-aminolevulinic acid in vitro cutaneous permeation and in vivo protoporphyrin IX accumulation determined by confocal microscopy. J. Controlled Release 65:359–366 (2000).Google Scholar
  69. 69.
    Z. Malik, G. Kostenich, L. Roitman, B. Ehrenberg, and A. Orenstein. Topical application of 5-aminolevulinic acid, DMSO, and EDTA: protoporphyrin IX accumulation in skin and tumors of mice. J. Photochem. Photobiol. B 28: 213–218 (1995).Google Scholar
  70. 70.
    Y. Harth, B. Hirshowitz, and B. Kaplan. Modified topical photodynamic therapy of superficial skin tumors, utilizing aminolevulinic acid, penetration enhancers, red light, and hyperthermia, Dermatol. Surg. 24: 723–726 (1998).Google Scholar
  71. 71.
    A. M. Soler, T. Warloe, J. Tausjo, and A. Berner. Photodynamic therapy by topical aminolevulinic acid, dimethylsulphoxide and curettage in nodularbasal cell carcinoma: a one-year follow-up study. Acta Derm. Venereol. (Stockh.) 79:204–206 (1999).Google Scholar
  72. 72.
    S. Fijan, H. Hönigsmann, and B. Ortel. Photodynamic therapy of epithelial skin tumours using delta-aminolevulinic acid and desferrioxamine. Br. J. Dermatol. 133:282–288 (1995).Google Scholar
  73. 73.
    D. Letourneur, C. Parisel, S. Pringent-Richard, and M. Cansell. Interactions of funcionalized dextran-coated liposomes with vascular smooth muscle cells. J. Controlled Release 65:83–91 (2000).Google Scholar
  74. 74.
    H. Fukuda, S. Paredes, and A.M. D. C. Batlle. Tumour-localizing properties of porphyrins. In vitro studies using porphyrin precursor, aminolevulinic acid, in free and liposome encapsulated forms. Drug. Des. Deliv. 5:133–139 (1989).Google Scholar
  75. 75.
    H. Fukuda, S. Paredes, and A.M. D. C. Batlle. Tumour-localizing properties of porphyrins. In vivo studies using free and liposome encapsulated aminolevulinic acid. Comp. Biochem. Physiol. 102B:433–436 (1992).Google Scholar
  76. 76.
    J. Kloek and G. M. J. B. Van Henegouwen. Prodrugs of 5-aminolevulinic acid for Photodynamic Therapy. Photochem. Photobiol. 64:994–1000 (1996).Google Scholar
  77. 77.
    Q. Peng, J. Moan, T. Warloe, V. Iani, H. B. Stenn, A. Bjørseth, and J. M. Nesland. Buid-up of esterified aminolevulinic-acid-derivative-induced porphyrin fluorescence in normal mouse skin. J. Photochem. Photobiol. B 34:95–96 (1996).Google Scholar
  78. 78.
    J.-M. Gaullier, K. Berg, Q. Peng, H. Anholt, P. K. Selbo, L.-W. Ma, and J. Moan. Use of 5-aminolevulinic acid esters to improve Photodynamic Therapy on cells in culture. Cancer Res. 57:1481–1486 (1997).Google Scholar
  79. 79.
    R. H. Guy, Y. N. Kalia, M. B. Delgado-Charro, V. Merino, A. Lopez, and D. Marro. Iontophoresis: electrorepulsion and electroosmosis. J. Controlled Release 64:129–132 (2000).Google Scholar
  80. 80.
    L. Rhodes, M. T. Tsoukas, R. R. Anderson, and N. Kollias. Iontophoretic delivery of ALA provides a quantitative model for ALA pharmacokinetics and PpIX phototoxicity in human skin. J. Invest. Dermatol. 108:87–91 (1997).Google Scholar
  81. 81.
    R. F. V. Lopez, M. V. L. B. Bentley, M. B. Delgado-Charro, and R. H. Guy. Iontophoretic delivery of 5-aminolevulinic acid (ALA): effect of pH. Proc. Int. Symp. Controlled Release Bioact. Mater. 27 (2000), in press.Google Scholar
  82. 82.
    L. Ma, J. Moan, Q. Peng, and V. Iani. Production of protoporphyrin IX induced by 5-aminolevulinic acid in transplanted human colonadenocarcinoma of nude mice can be increased by ultrasound. Int. J. Cancer 78:464–469 (1998.).Google Scholar
  83. 83.
    N. Van Der Veen, H. S. De Bruijn, and W. M. Star. Photobleaching during and re-appearance after photodynamic therapy of topical 5-ALA-induced fluorescence in UVB-treated mouse skin. Int. J. Cancer 72:110–118 (1997).Google Scholar
  84. 84.
    H. Messmann, P. Mlkvy, G. Buonaccorso, C. L. Davies, A. J. Macrobert, and S. G. Bown. Enhancement of photodynamic therapy with 5-aminolevulinic acid-induced porphyrin photosensitisation in normal rat colon by threshold and light fractionation studies. Br. J. Cancer 72:589–594 (1995).Google Scholar
  85. 85.
    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. 69:71–76 (1999).Google Scholar
  86. 86.
    H. S. De Bruijn, N. Van der Veen, D. J. Robinson, and W. M. Star. Improvement of systemic 5-aminolevulinic acid-based photodynamic therapy in vivo using light fractionation with a 75-minute interval. Cancer Res. 59:901–904 (1999).Google Scholar
  87. 87.
    J. Moan, K. Berg, O. Gadmar, V. Biani, L. Ma, and P. Juzenas. The temperature dependence of protoporphyrin IX production in cells and tissues. Photochem. Photobiol. 70:669–673 (1999).Google Scholar
  88. 88.
    P. Juzenas, R. Sorensen, V. Iani, and J. Moan. Uptake of topically applied of 5-aminolevulinic acid and production of protoporphyrin IX in normal mouse skin: dependence on skin temperature. Photochem. Photobiol. 69:478–481 (1999).Google Scholar

Copyright information

© Plenum Publishing Corporation 2000

Authors and Affiliations

  • Fernanda S. De Rosa
    • 1
  • M. Vitória L. B. Bentley
    • 1
    • 2
  1. 1.Department of Pharmaceuticals SciencesUniversity of São Paulo, Ribeirão PretoSão PauloBrazil
  2. 2.Faculdade de Ciěncias FarmacěuticasSão PauloBrazil

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