Skip to main content
Log in

Photodynamic therapy of experimental colonic tumours with 5-aminolevulinic-acid-induced endogenous porphyrins

  • Original Papers
  • Experimental Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

5-Aminolevulinic acid (5-ALA) is a precursor in the biosynthesis of haem. External application of 5-ALA leads to the formation of protoporphyrin IX, the last intermediate product before haem, which is an effective sensitiser. The 5-ALA-induced endogenous photosensitisation of tumour cells has been exploited for photodynamic therapy (PDT). Experimental human G-3 colonic tumours were transplanted into nude mice, and ten mice were treated by PDT. Ten animals served as controls. We measured a fluorescence intensity of the tumour that was about eight times higher than in the surrounding tissue; a good correlation between the fluorescence intensity and the photodynamic effect was found. Tumour growth was inhibited significantly after PDT, two tumours being destroyed completely after the second PDT treatment. In addition, on-line fluorescence detection during PDT showed a change in the intensity and the fluorescence spectrum of protoporphyrin IX caused by photobleaching and the formation of photoproducts.

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

  • Barr H, Tralau CJ, MacRobert AJ, Morrison I, Phillips D, Bown SG (1988) Fluorescence photometric techniques for determination of microscopic tissue distribution of phthalocyanine photosensitizers for photodynamic therapy. Lasers Med Sci 3:81–86

    Google Scholar 

  • Barr H, Chatlani P, Tralau CJ, MacRobert AJ, Boulos PB, Bown SG (1991) Local eradication of rat colon cancer with photodynamic therapy: correlation of distribution of photosensitiser with biological effects in normal and tumour tissue. Gut 32:517–523

    Google Scholar 

  • Bedwell J, MacRobert AJ, Phillips D, Bown SG (1992) Fluorescence distribution and photodynamic effect of ALA-induced PP IX in the DMH rat colonic tumour model. Br J Cancer 65:818–824

    Google Scholar 

  • Charlsworth P, Truscott TG (1993) The use of 5-aminolevulinic acid (ALA) in photodynamic therapy (PDT). J Photochem Photobiol [B] 18:99–100

    Google Scholar 

  • Divaris DXG, Kennedy JC, Pottier RH (1990) Phototoxic damage to sebaceous glands and hair follicles of mice after systemic administration of 5-aminolevulinic acid correlates with localized protoprophyrin IX fluorescence. Am J Pathol 136:891–897

    Google Scholar 

  • Henderson BW, Waldow SM, Mang TS, Potter WR, Malone B, Doughtery TJ (1985) Tumor destruction and kinetics of tumor cell death in two experimental mouse tumors following PDT. Cancer Res 45:572–576

    Google Scholar 

  • Inhoffen HH, Brockmann H, Bliesener KM (1969) Photoprotoporpyrine und ihre Umwandlung in Spirographis sowie Isospirographis-Porphirin. Liebigs Ann Chem 730:173–185

    Google Scholar 

  • Kelly JF, Snell ME, Berembaum MC (1975) Photodynamic destruction of human bladder carcinoma. Br J Cancer 31:237–244

    Google Scholar 

  • Kennedy JC, Pottier RH (1992) Endogenous protoporphyrin IX, a clinical useful photosensitizer for photodynamic therapy. J Photochem Photobiol [B] 14:275–292

    Google Scholar 

  • Kennedy JC, Pottier RH, Pross DC (1990) Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience. J Photoechem Photobiol [B] 6:143–148

    Google Scholar 

  • König K, Wabnitz H, Dietel W (1990) Variation in the fluorescence decay properties of hematoporphyrin derivative during its conversion into photoproducts. J Photochem Photobiol [B] 8:103–111

    Google Scholar 

  • König K, Schneckenburger H, Rück A, Steiner R (1993) In vivo photoproducts formation during PDT with ALA-induced endogenous porphyrins. J Photochem Photobiol [B] 18:287–290

    Google Scholar 

  • Loh CS, MacRobert AJ, Bedwell J, Regula J, Krasner N, Bown SG (1993) Oral versus intravenous administration of 5-amino-levulinic acid for photodynamic therapy. Br J Cancer 68:41–51

    Google Scholar 

  • Malik Z, Djaldetti M (1979) 5-Aminolevulinic acid stimulation of porphyrin and hemoglobin synthesis by uninduced fried erythroleukaemic cells. Cell Differ 8:223–233

    Google Scholar 

  • McGilvery RW, Goldstein G (eds) (1979) Biochemistry, functional approach. Saunders, Philadelphia London Toronto, pp 632–635

    Google Scholar 

  • Peng Q, Moan J, Warloe T, Nesland JM, Rimington C (1992) Distribution and photosensitizing efficiency or porphyrins induced by application of exogenous 5-aminolevulinic acid in mice bearing mammary carcinoma. Int J Cancer 52:433–443

    Google Scholar 

  • Schneckenburger H, Strauss W, Rück A, Seidlitz H, Wessels JM (1992) Microscopic fluorescence spectroscopy and diagnosis. Opt Eng 31:995–999

    Google Scholar 

  • Seidlitz HK, Stettmaier K, Wessels JM, Schneckenburger H (1992) Intracellular fluorescence polarization, picosecond kinetics and light-induced reactions of photosensitizing porphyrins. Opt Eng 31:1482–1486

    Google Scholar 

  • Sima AAF, Kennedy JC, Blakeslee D, Robertson DM (1981) Experimental porphyric neuropathy: a preliminary report. Can J Neurol Sci 8:105–113

    Google Scholar 

  • Valat P, Reinhart GD, Jameson DM (1988) Application of time-resolved fluorometry to the resolution of porphyrine-product mixtures. Photochem Photobiol [B] 47:787–790

    Google Scholar 

  • Yamashita M, Jomura M, Kobayashi S, Sato T (1984) Picosecond time resolved fluorescence spectroscopy of HPD. IEEE J Quantum Electron 20:1363–1369

    Google Scholar 

  • Zalar GL, Poh-Fitzpatrick M, Krohn DL, Jacobs R, Harber LC (1977) Induction of drug photosensitisation in man after parenteral exposure to hematoporphyrin. Arch Dermatol 113:1392–1397

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Orth, K., König, K., Genze, F. et al. Photodynamic therapy of experimental colonic tumours with 5-aminolevulinic-acid-induced endogenous porphyrins. J Cancer Res Clin Oncol 120, 657–661 (1994). https://doi.org/10.1007/BF01245377

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01245377

Key words

Navigation