Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 2001 Nov;85(11):1794–1800. doi: 10.1054/bjoc.2001.2156

ALA and ALA hexyl ester-induced porphyrin synthesis in chemically induced skin tumours: the role of different vehicles on improving photosensitization

A Casas 1, C Perotti 1, H Fukuda 1, L Rogers 2, A R Butler 2, A Batlle 1
PMCID: PMC2363985  PMID: 11742504

Abstract

Exogenous administration of 5-aminolevulinic acid (ALA) is becoming widely used to enhance the endogenous synthesis of Protoporphyrin IX (PpIX) in photodynamic therapy. We analysed porphyrin formation in chemically induced squamous papillomas, after topical application of ALA and ALA hexyl ester (He-ALA) administered in different formulations, as well as the pattern of distribution in the internal organs, and the synthesis of porphyrins in distant tumoural and normal skins. A lotion formulation containing DMSO and ethanol was the best vehicle for topical ALA delivery to papillomas, whereas cream was the most efficient formulation for He-ALA application. Similar porphyrin concentration can be accumulated in the skin tumours employing either ALA or He-ALA delivered in their optimal formulations. The use of cream as a vehicle of both ALA and He-ALA, induces highest porphyrin tumour/normal skin ratios. The main advantage of using He-ALA is that porphyrins synthesized from the ester are more confined to the site of application, thus inducing low porphyrin levels in normal skin, liver, blood and spleen, as well as in papillomas distant from the point of application, independently on the vehicle employed, so reducing potential side effects of photodynamic therapy. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords: ALA, ALA esters, photodynamic therapy, squamous papillomas

Full Text

The Full Text of this article is available as a PDF (150.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Boehncke W. H., Sterry W., Kaufmann R. Treatment of psoriasis by topical photodynamic therapy with polychromatic light. Lancet. 1994 Mar 26;343(8900):801–801. doi: 10.1016/s0140-6736(94)91883-x. [DOI] [PubMed] [Google Scholar]
  2. Burns F., Albert R., Altshuler B., Morris E. Approach to risk assessment for genotoxic carcinogens based on data from the mouse skin initiation-promotion model. Environ Health Perspect. 1983 Apr;50:309–320. doi: 10.1289/ehp.8350309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Casas A., Batlle A. M., Butler A. R., Robertson D., Brown E. H., MacRobert A., Riley P. A. Comparative effect of ALA derivatives on protoporphyrin IX production in human and rat skin organ cultures. Br J Cancer. 1999 Jul;80(10):1525–1532. doi: 10.1038/sj.bjc.6690556. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Casas A., Fukuda H., Batlle A. M. Tissue distribution and kinetics of endogenous porphyrins synthesized after topical application of ALA in different vehicles. Br J Cancer. 1999 Sep;81(1):13–18. doi: 10.1038/sj.bjc.6690644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Casas A., Fukuda H., Di Venosa G., Batlle A. M. The influence of the vehicle on the synthesis of porphyrins after topical application of 5-aminolaevulinic acid. Implications in cutaneous photodynamic sensitization. Br J Dermatol. 2000 Sep;143(3):564–572. doi: 10.1111/j.1365-2133.2000.03711.x. [DOI] [PubMed] [Google Scholar]
  6. Fritsch C., Lang K., Neuse W., Ruzicka T., Lehmann P. Photodynamic diagnosis and therapy in dermatology. Skin Pharmacol Appl Skin Physiol. 1998 Nov-Dec;11(6):358–373. doi: 10.1159/000029858. [DOI] [PubMed] [Google Scholar]
  7. Fukuda H., Paredes S., Batlle A. M. Tumour-localizing properties of porphyrins. In vivo studies using free and liposome encapsulated aminolevulinic acid. Comp Biochem Physiol B. 1992 Jun;102(2):433–436. doi: 10.1016/0305-0491(92)90147-j. [DOI] [PubMed] [Google Scholar]
  8. Gaullier J. M., Berg K., Peng Q., Anholt H., Selbo P. K., Ma L. W., Moan J. Use of 5-aminolevulinic acid esters to improve photodynamic therapy on cells in culture. Cancer Res. 1997 Apr 15;57(8):1481–1486. [PubMed] [Google Scholar]
  9. Kennedy J. C., Pottier R. H., Pross D. C. Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience. J Photochem Photobiol B. 1990 Jun;6(1-2):143–148. doi: 10.1016/1011-1344(90)85083-9. [DOI] [PubMed] [Google Scholar]
  10. Kloek J., Akkermans W., Beijersbergen van Henegouwen G. M. Derivatives of 5-aminolevulinic acid for photodynamic therapy: enzymatic conversion into protoporphyrin. Photochem Photobiol. 1998 Jan;67(1):150–154. [PubMed] [Google Scholar]
  11. Kloek J., Beijersbergen van Henegouwen Prodrugs of 5-aminolevulinic acid for photodynamic therapy. Photochem Photobiol. 1996 Dec;64(6):994–1000. doi: 10.1111/j.1751-1097.1996.tb01868.x. [DOI] [PubMed] [Google Scholar]
  12. Kurwa H. A., Barlow R. J. The role of photodynamic therapy in dermatology. Clin Exp Dermatol. 1999 May;24(3):143–148. doi: 10.1046/j.1365-2230.1999.00439.x. [DOI] [PubMed] [Google Scholar]
  13. Peng Q., Moan J., Warloe T., Iani V., Steen H. B., Bjørseth A., Nesland J. M. Build-up of esterified aminolevulinic-acid-derivative-induced porphyrin fluorescence in normal mouse skin. J Photochem Photobiol B. 1996 Jun;34(1):95–96. doi: 10.1016/1011-1344(95)07268-3. [DOI] [PubMed] [Google Scholar]
  14. Peng Q., Warloe T., Moan J., Heyerdahl H., Steen H. B., Nesland J. M., Giercksky K. E. Distribution of 5-aminolevulinic acid-induced porphyrins in noduloulcerative basal cell carcinoma. Photochem Photobiol. 1995 Nov;62(5):906–913. doi: 10.1111/j.1751-1097.1995.tb09154.x. [DOI] [PubMed] [Google Scholar]
  15. van den Akker J. T., Iani V., Star W. M., Sterenborg H. J., Moan J. Topical application of 5-aminolevulinic acid hexyl ester and 5-aminolevulinic acid to normal nude mouse skin: differences in protoporphyrin IX fluorescence kinetics and the role of the stratum corneum. Photochem Photobiol. 2000 Nov;72(5):681–689. doi: 10.1562/0031-8655(2000)072<0681:taoaah>2.0.co;2. [DOI] [PubMed] [Google Scholar]
  16. van den Akker J. T., de Bruijn H. S., Beijersbergen van Henegouwen G. M., Star W. M., Sterenborg H. J. Protoporphyrin IX fluorescence kinetics and localization after topical application of ALA pentyl ester and ALA on hairless mouse skin with UVB-induced early skin cancer. Photochem Photobiol. 2000 Sep;72(3):399–406. doi: 10.1562/0031-8655(2000)072<0399:pifkal>2.0.co;2. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES