Endogenous porphyrin distribution induced by 5-aminolaevulinic acid in the tissue layers of the gastrointestinal tract.

The accumulation of endogenous porphyrins in rats following systemic administration of 5-aminolaevulinic acid (ALA) has been examined to assess the photosensitization characteristics of this technique for photodynamic therapy (PDT) and chemical extraction assays with fluorescence and absorbance detection of the porphyrin content have been carried out. We compared the results obtained using quantitative microfluorimetry on normal gastric and colonic tissues in rats at 0.5, 1, 2, 4 and 6 h and chemically induced duodenal tumours 2 and 4.5 h after intravenous administration of ALA at a dose of 200 mg kg-1. With chemical extraction followed by high performance liquid chromatography analysis, protoporphyrin IX (PpIX) was found to be the predominant porphyrin present, reaching peak levels of several microgrammes per gramme at 2-4 h in each type of tissue; a small amount of coproporphyrin was detected at 0.5 and 2 h in normal gastric mucosa and duodenal tumour respectively. Both the extraction assay and quantitative microfluorimetry showed that the porphyrin fluorescence builds up rapidly in the mucosal layers of the colon and stomach, reaching a maximum at 2 h, whereas lower fluorescence levels were found with a slower rate of accumulation in the corresponding muscularis layers. A significant PpIX content was found in the duodenal tumour, with a maximum of 7.1 micrograms g-1 4.5 h after ALA administration. We conclude that systemic administration of ALA can induce effective tissue sensitization with protoporphyrin IX and appears to be a promising technique for PDT.

[1]  T. Sugimura,et al.  Sequential morphological changes in N-methyl-N'-nitro-N-nitrosoguanidine carcinogenesis in the glandular stomach of rats. , 1970, Journal of the National Cancer Institute.

[2]  S. G. Bown,et al.  Photodynamic therapy of the normal rat stomach: a comparative study between di-sulphonated aluminium phthalocyanine and 5-aminolaevulinic acid. , 1992, British Journal of Cancer.

[3]  Z. Malik,et al.  5-Aminolevulinic acid stimulation of porphyrin and hemoglobin synthesis by uninduced Friend erythroleukemic cells. , 1979, Cell differentiation.

[4]  N. Navone,et al.  Heme biosynthesis in human breast cancer--mimetic "in vitro" studies and some heme enzymic activity levels. , 1990, The International journal of biochemistry.

[5]  H. Barr,et al.  COMPARISON OF DISTRIBUTION AND PHOTODYNAMIC EFFECTS OF DI‐ AND TETRA‐SULPHONATED ALUMINIUM PHTHALOCYANINES IN NORMAL RAT COLON , 1991, Photochemistry and photobiology.

[6]  J C Kennedy,et al.  NON‐INVASIVE TECHNIQUE FOR OBTAINING FLUORESCENCE EXCITATION AND EMISSION SPECTRA IN VIVO , 1986, Photochemistry and photobiology.

[7]  R. van Hillegersberg,et al.  Selective accumulation of endogenously produced porphyrins in a liver metastasis model in rats. , 1992, Gastroenterology.

[8]  J. Kennedy,et al.  Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience. , 1990, Journal of photochemistry and photobiology. B, Biology.

[9]  A E Profio,et al.  SKIN PHOTOSENSITIVITY: DURATION and INTENSITY FOLLOWING INTRAVENOUS HEMATOPORPHYRIN DERIVATES, HpD and DHE , 1987, Photochemistry and photobiology.

[10]  Robert E. Anderson,et al.  Hematoporphyrin derivative: Quantitative uptake in dimethylhydrazine‐induced murine colorectal carcinoma , 1983, Journal of surgical oncology.

[11]  J C Kennedy,et al.  Phototoxic damage to sebaceous glands and hair follicles of mice after systemic administration of 5-aminolevulinic acid correlates with localized protoporphyrin IX fluorescence. , 1990, The American journal of pathology.

[12]  T. Dougherty,et al.  Determination of [3H]- and [14C]hematoporphyrin derivative distribution in malignant and normal tissue. , 1979, Cancer research.

[13]  C. Byrne,et al.  The composition of Photofrin II. , 1990, Journal of photochemistry and photobiology. B, Biology.

[14]  T. Dougherty Photosensitization of malignant tumors. , 1986, Seminars in surgical oncology.

[15]  D. Phillips,et al.  Fluorescence distribution and photodynamic effect of ALA-induced PP IX in the DMH rat colonic tumour model. , 1992, British Journal of Cancer.

[16]  A. J. MacRobert,et al.  Oral versus intravenous administration of 5-aminolaevulinic acid for photodynamic therapy. , 1993, British Journal of Cancer.

[17]  J Moan,et al.  Distribution and photosensitizing efficiency of porphyrins induced by application of exogenous 5‐aminolevulinic acid in mice bearing mammary carcinoma , 1992, International journal of cancer.

[18]  Z. Malik,et al.  Destruction of erythroleukaemic cells by photoactivation of endogenous porphyrins. , 1987, British Journal of Cancer.