Biochemical basis of 5-aminolaevulinic acid-induced protoporphyrin IX accumulation: a study in patients with (pre)malignant lesions of the oesophagus

Br J Cancer. 1998 Sep;78(5):679-82. doi: 10.1038/bjc.1998.559.

Abstract

Administration of 5-aminolaevulinic acid (ALA) leads to porphyrin accumulation in malignant and premalignant tissues, and ALA is used as a prodrug in photodynamic therapy (PDT). To understand the mechanism of porphyrin accumulation after the administration of ALA and to investigate whether ALA-induced protoporphyrin IX might be a suitable photosensitizer in Barrett's oesophagus and adenocarcinoma, we determined the activities of porphobilinogen deaminase (PBG-D) and ferrochelatase (FC) in various malignant and premalignant as well as in normal tissues of the human oesophagus. A PDT power index for ALA-induced porphyrin accumulation, the ratio of PBG-D to FC normalized for the normal squamous epithelium of the oesophagus, was calculated to evaluate intertissue variation in the ability to accumulate porphyrins. In malignant and premalignant tissue a twofold increased PBG-D activity and a marginally increased FC activity was seen compared with normal squamous epithelium. A significantly increased PDT power index in Barrett's epithelium and adenocarcinoma was found. Our results suggest that, after the administration of ALA, porphyrins will accumulate in a greater amount in Barrett's epithelium and adenocarcinoma of the oesophagus because of an imbalance between PBG-D and FC activities. The PDT power index here defined might be a useful indicative parameter for predicting the susceptibility of these tissues to ALA-PDT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aminolevulinic Acid / pharmacology
  • Aminolevulinic Acid / therapeutic use*
  • Barrett Esophagus / drug therapy*
  • Barrett Esophagus / metabolism
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / metabolism
  • Esophagus / enzymology
  • Female
  • Ferrochelatase / metabolism
  • Humans
  • Hydroxymethylbilane Synthase / metabolism
  • Male
  • Middle Aged
  • Photochemotherapy*
  • Photosensitizing Agents
  • Precancerous Conditions / drug therapy*
  • Precancerous Conditions / metabolism
  • Prodrugs / therapeutic use*
  • Protoporphyrins / biosynthesis*

Substances

  • Photosensitizing Agents
  • Prodrugs
  • Protoporphyrins
  • Aminolevulinic Acid
  • protoporphyrin IX
  • Hydroxymethylbilane Synthase
  • Ferrochelatase