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The use of 5-aminolaevulinic acid (ALA) is gaining increasing attention for photosensitization in photodynamic therapy of superficially localized tumours. The aim of this work was to determine the kinetics of porphyrin generation in tissues after topical application of ALA delivered in different vehicles on the skin overlying the tumour and normal skin of mice. Maximal accumulation was found in tumour 3 h after ALA application in both cream and lotion preparations. Normal and overlying tumour skin tissues showed different kinetic patterns, reflecting histological changes when the latter is invaded by tumour cells. Liver, kidney, spleen and blood porphyrins also raised from basal levels, showing that ALA and/or ALA-induced porphyrins reach all tissues after topical application. During the first 24 h of ALA topical application, precursors and porphyrins are excreted by both urine and faeces. ALA lotion applied on the skin overlying the tumour induced higher accumulation of tumoural porphyrins than cream, and lotion applied on normal skin appeared to be the most efficient upon inducing total body porphyrins. This work has demonstrated the great influence of the formulation of ALA vehicle on penetration through the skin. Knowledge of the kinetics of porphyrin generation after different conditions of ALA application is needed for the optimization of diagnosis and phototherapy in human tumours.


Documento: Artículo
Título:Tissue distribution and kinetics of endogenous porphyrins synthesized after topical application of ALA in different vehicles
Autor:Casas, A.; Fukuda, H.; Del C Batlle, A.M.
Filiación:Ctro. de Invest. sobre P., FCEyN, University of Buenos Aires, (142B) Capital Federal, Argentina
Viamonte 1881 10A, 1056 Buenos Aires, Argentina
Palabras clave:5-Aminolaevulinic acid; ALA cream; ALA lotion; ALA-PDT; Topical application; aminolevulinic acid; drug vehicle; photosensitizing agent; porphyrin; animal experiment; animal model; animal tissue; article; cancer therapy; controlled study; cream; feces level; kidney; kinetics; liver; lotion; male; mouse; nonhuman; photodynamic therapy; priority journal; skin; spleen; tissue distribution; topical drug administration; urine level; Adenocarcinoma; Administration, Topical; Aminolevulinic Acid; Animals; Kinetics; Male; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Photosensitizing Agents; Porphyrins; Tissue Distribution; Vehicles
Página de inicio:13
Página de fin:18
Título revista:British Journal of Cancer
Título revista abreviado:Br. J. Cancer
CAS:Aminolevulinic Acid, 106-60-5; Photosensitizing Agents; Porphyrins; Vehicles


  • Batlle, A., Grinstein, M., Porphyrin biosynthesis. Studies on the nature of a biosynthetic porphyrin and its identification with the so-called "208" porphyrin (1962) Biochim Biophys Acta, 57, pp. 191-194
  • Batlle, A., Llambías, E., Wider, E., Tigier, H., Porphyrin biosynthesis in the soybean callus tissue system XV. The effect of growth conditions (1975) Int J Biochem, 6, pp. 591-606
  • Dailey, H., Smith, A., Differential interaction of porphyrins used in photoradiation therapy with ferrochelatase (1984) Biochem J, 223, pp. 441-445
  • Doss, M., Schmidt, A., Rapid determination of urinary total porphyrins by ion exchange chromatography (1971) Z Klin Chem Klin Biochem, 9, pp. 415-418
  • Doss, M., Schmidt, A., Quanlitative bestimmung der 5-aminolävulinsäure und porphobilinogen im urin mit lonenaustauschereromathographic-fertigsäulen (1971) Z Klin Chem Klin Biochem, 9, pp. 99-102
  • Dougherty, T., Grindey, G., Fiel, R., Weishaupt, K., Boyle, D., Photoradiation therapy II: Cure of animal tumours with hematoporphyrin and light (1975) J Natl Cancer Inst, 55, pp. 115-121
  • Falk, J., Porphyrins and metalloporphyrins (1964) Biochimica of Biophysica Acta Library, 2. , Elsevier: Amsterdam
  • Fritsch, C., Verwohlt, B., Bolsen, K., Ruzicka, T., Goerz, G., Influence of topical photodynamic therapy with 5-aminolevulinic acid on porphyrin metabolism (1996) Arch Dermatol Res, 288, pp. 517-521
  • Fukuda, H., Paredes, S., Batlle, A., Tumour-localizing properties of porphyrins. In vitro studies using the porphyrin precursor, aminolevulinic acid, in free and liposome encapsulated forms (1989) Drug Des Deliv, 5, pp. 133-139
  • Fukuda, H., Paredes, S., Batlle, A., Tumour-localizing properties of porphyrins. In vivo studies using free and liposome encapsulated aminolevutinic acid (1992) Comp Biochem Physiol, 102 B, pp. 433-436
  • Fukuda, H., Batlle, A., Riley, P., Kinetics of porphyrin accumulation in cultured epithelial cells exposed to ALA (1993) Int J Biochem, 25, pp. 1407-1410
  • Goof, B., Bachor, R., Kollias, N., Hasan, T., Effects of photodynamic therapy with topical application of 5-aminolevulinic acid on normal skin of hairless guinea pigs (1992) J Photochem Photobiol, 15, pp. 239-251
  • Grant, W., Hopper, C., MacRobert, A., Speight, P., Bown, S., Photodynamic therapy of oral cancer: Photosensitization with systemic aminolevulinic acid (1993) Lancet, 342, pp. 147-148
  • Henderson, B.W., Vaughan, I., Bellnier, D., Van Leengoed, H., Johnson, P.G., Oseroff, A.R., Photosensitization of murine tumour, vasculature and skin by 5-aminolevulinic acid-induced porphyrin (1995) Photochem Photobiol, 62, pp. 780-789
  • Kennedy, J., Pottier, R., Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy (1992) J Photochem Photobiol B, 14, pp. 275-292
  • Kennedy, J., Pottier, R., Pross, G., Photodynamic therapy with endogenous protoporphyrin IX: Basic principles and present clinical experience (1990) J Photochem Photobiol B, 6, pp. 143-148
  • Kriegmair, M., Baumgartner, R., Knuechel, R., Stepp, H., Hofstädter, F., Hofstetter, A., Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence (1996) J Urology, 155, pp. 105-110
  • Magee, P., Percutaneous absorption: Critical factors in transdermal transport (1991) Dermatoxicology, pp. 1-35. , Marzulli F and Maibach H (eds). Hemisphere: New York
  • Menon, J., Becker, S., Persad, S., Haberman, H., Quantitation of hydrogen peroxide formed during UV-visible irradiation of protoporphyrin, coproporphyrin and uroporphyrin (1990) Clin Chim Acta, 186, pp. 375-381
  • Navone, N., Frisardi Resnik, E., Batlle, A., Polo, C., Porphyrin biosynthesis in human breast cancer. Preliminary mimetic in vitro studies (1988) Med Sci Res, 16, pp. 61-62
  • Navune, N., Polo, C., Frisardi, A., Batlle, A., Mouse mammary carcinoma PBGase and hydroxymethylbilane synthetase (1991) Comp Biochem Physiol B, 98, pp. 67-71
  • Peng, Q., Moan, J., Warloc, T., Nesland, J.M., Rimington, C., Distribution and photosensitizing efficiency of porphyrins induced by application of exogenous 5-aminolevulinic acid in mice bearing mammary carcinoma (1992) Int J Cancer, 52, pp. 433-443
  • Rougier, A., Lotte, C., Correlations between horny layer concentration and percutaneous absorption (1986) Pharmacology and Skin: I. Skin Pharmacokinetics, , Shroot B (ed) Schaeger: Switzerland
  • Schoenfeld, N., Epstein, O., Lahav, M., Mamet, R., Shaklai, M., Atsmon, A., The heme biosynthetic pathway in lymphocytes of patients with malignant lymphoproliferative disorders (1998) Cancer Lett, 43, pp. 43-48
  • Schoenfeld, N., Mamet, R., Nordenberg, Y., Shafran, M., Babushkin, T., Malik, Z., Protoporphyrin biosynthesis in melanoma B16 cells stimulated by 5-aminolaevulinic acid and chemical inducers: Characterization of photodynamic inactivation (1994) Int J Cancer, 56, pp. 106-112
  • Scolnik, A., Rubio, M., Colombo, L., Comolli, R., Caro, R., Further studies on the bystamine metabolism in the M2 adenocarcinoma (1984) Biomed Pharmacother, 38, pp. 465-467
  • Stringer, M., Collins, P., Robinson, D., Stabhles, G., Sheehan-Dare, R., The accumulation of Protoporphyrin IX in plaque psoriasis after topical application of 5-aminolevulinic acid indicates a potential for superficial photodynamic therapy (1996) J Invest Dermatol, 107, pp. 76-81
  • Torralba Rodriguez, A., Histologia y fisiologia de la piel y sus anejos. Aspectos básicos e implicaciones cosméticas (1985) Cosmetología Teórico-prática, pp. 13-46. , Consejo General de Colegios Oficiales de Farmacéuticos: Madrid
  • (1988) UKCCCR Guidelines for the Welfare of Animals in Experimental Neoplasia, , UKCCCR: London
  • Van Hillesberg, R., Van Der Berg, J., Kort, W., Terpstra, O., Wilson, J., Selective accumulation of endogenously produced porphyrins in a liver metastasis model in rats (1992) Gastroenterology, 103, pp. 647-651
  • With, T., Clinical use of porphyrin ester cromatography in urine and feces (1975) Dan Med Bull, 22, p. 74
  • Wolf, P., Rieger, F., Kerl, H., Topical photodynamic therapy with endogenous porphyrins after application of 5-aminolevulíníc acíd (1993) J Am Acad Dermatol, 28, pp. 17-21


---------- APA ----------
Casas, A., Fukuda, H. & Del C Batlle, A.M. (1999) . Tissue distribution and kinetics of endogenous porphyrins synthesized after topical application of ALA in different vehicles. British Journal of Cancer, 81(1), 13-18.
---------- CHICAGO ----------
Casas, A., Fukuda, H., Del C Batlle, A.M. "Tissue distribution and kinetics of endogenous porphyrins synthesized after topical application of ALA in different vehicles" . British Journal of Cancer 81, no. 1 (1999) : 13-18.
---------- MLA ----------
Casas, A., Fukuda, H., Del C Batlle, A.M. "Tissue distribution and kinetics of endogenous porphyrins synthesized after topical application of ALA in different vehicles" . British Journal of Cancer, vol. 81, no. 1, 1999, pp. 13-18.
---------- VANCOUVER ----------
Casas, A., Fukuda, H., Del C Batlle, A.M. Tissue distribution and kinetics of endogenous porphyrins synthesized after topical application of ALA in different vehicles. Br. J. Cancer. 1999;81(1):13-18.