The stability of 5-aminolevulinic acid in solution.

5-Aminolevulinic acid (ALA) is being assessed for photodynamic therapy of cancer and other diseases worldwide. However, its stability properties in solution are not well understood yet. The breakdown of ALA in pH-buffered solutions was examined in this work. Solutions of ALA in PBS buffered to physiological pH were found to be unstable, leading to a breakdown product that absorbs photons around 278 nm. The ability of the solution to stimulate porphyrin production in cells is gradually lost upon breakdown, though the kinetics for this are different from those for formation of the UV absorbing product. It is likely, therefore, that several chemical pathways contribute to the breakdown of dissolved ALA at physiological pH. Temperature studies of the formation kinetics of the UV absorbing product also indicate that a complex formation process is involved.

[1]  G Hüttmann,et al.  Chemical instability of 5-aminolevulinic acid used in the fluorescence diagnosis of bladder tumours. , 1996, Journal of photochemistry and photobiology. B, Biology.

[2]  A. Vercesi,et al.  Damage to rat liver mitochondria promoted by delta-aminolevulinic acid-generated reactive oxygen species: connections with acute intermittent porphyria and lead-poisoning. , 1991, Biochimica et biophysica acta.

[3]  K. Berg,et al.  The influence of iron chelators on the accumulation of protoporphyrin IX in 5-aminolaevulinic acid-treated cells. , 1996, British Journal of Cancer.

[4]  J Moan,et al.  5‐Aminolevulinic acid‐based photodynamic therapy , 1997, Cancer.

[5]  C. Gomer,et al.  Photodynamic therapy of intraocular tumors: examination of hematoporphyrin derivative distribution and long-term damage in rabbit ocular tissue. , 1985, Cancer research.

[6]  H Anholt,et al.  Use of 5-aminolevulinic acid esters to improve photodynamic therapy on cells in culture. , 1997, Cancer research.

[7]  Kristian Berg,et al.  Protoporphyrin IX accumulation in cells treated with 5‐aminolevulinic acid: Dependence on cell density, cell size and cell cycle , 1998, International journal of cancer.

[8]  S. Granick,et al.  Pbrphyrin biosynthesis in erythrocytes. II. Enzymes converting gamma-aminolevulinic acid to coproporphyrinogen. , 1958, The Journal of biological chemistry.

[9]  Z. Malik,et al.  Topical application of 5-aminolevulinic acid, DMSO and EDTA: protoporphyrin IX accumulation in skin and tumours of mice. , 1995, Journal of photochemistry and photobiology. B, Biology.

[10]  Q. Peng,et al.  5‐Aminolevulinic Acid‐Based Photodynamic Therapy: Principles and Experimental Research , 1997, Photochemistry and photobiology.

[11]  A. Butler,et al.  The nonenzymatic cyclic dimerisation of 5-aminolevulinic acid , 1992 .

[12]  S. Iinuma,et al.  A mechanistic study of cellular photodestruction with 5-aminolaevulinic acid-induced porphyrin. , 1994, British Journal of Cancer.

[13]  Henry W. Lim,et al.  EFFECT OF UVA AND BLUE LIGHT ON PORPHYRIN BIOSYNTHESIS IN EPIDERMAL CELLS * , 1993, Photochemistry and photobiology.

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

[15]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.