Elsevier

Journal of Surgical Research

Volume 68, Issue 1, 15 February 1997, Pages 31-37
Journal of Surgical Research

Regular Article
Side Effects and Photosensitization of Human Tissues after Aminolevulinic Acid

https://doi.org/10.1006/jsre.1997.5004Get rights and content

Abstract

Aminolevulinic acid (ALA) is being used as a “pro-drug” for photodynamic therapy. The side effects of ALA have been only anecdotally reported and these effects as well as pharmacokinetics of the photosensitizing end product of ALA, protoporphyrin IX (PpIX), in patients undergoing operation are unknown. This study systematically determines the side effects of ALA and pharmacokinetics of PpIX in patients undergoing abdominal surgery. Patients were given 30 or 60 mg/kg ALA preoperatively, kept in subdued light for 48 hr, and monitored clinically and with laboratory tests for 5 to 7 days and for at least 2 months thereafter. Periodic plasma samples and tissue biopsies were analyzed for PpIX concentrations using a photodiode array system. No patient developed symptoms of porphyria other than nausea and vomiting, which occurred in 20%. Nearly one-quarter of patients developed transient abnormal liver functions. No patient developed cutaneous phototoxicity, abnormal neurologic function, or unexpected postoperative laboratory tests. The times of peak plasma, skin, skeletal muscle, omental, mucosal, muscularis mucosal, and tumor concentrations of PpIX varied among patients. In general, PpIX concentrations were significantly greater with the higher dose of ALA. Tumor PpIX concentrations were significantly greater than in other tissues except liver. In conclusion, ALA, up to 60 mg/kg, is associated with minimal side effects in patients undergoing operation. Actual tissue concentrations of PpIX suggest that endogenous photosensitization using systemically administered ALA is a mode of PDT feasible for treatment of adenocarcinomas of the gastrointestinal tract in humans.

References (35)

  • J.A. Stein et al.

    Abnormal iron and water metabolism in acute intermittent prophyria with new morphologic findings

    Am. J. Med.

    (1972)
  • S. Iinuma et al.

    Biodistribution and phototoxicity of 5-aminolevulinic acid-induced PpIX in an orthotopic rat bladder tumor model

    J. Urol.

    (1995)
  • B.W. Henderson et al.

    Photosensitization of murine tumor, vasculature and skin by 5-aminolevulinic acid-induced porphyrin

    Photochem. Photobiol.

    (1995)
  • D.J.H. Roberts et al.

    Tumour vascular shutdown following photodynamic therapy based on polyhaematoporphyrin or 5-aminolevululinic acid

    Int. J. Oncol.

    (1994)
  • W.E. Star et al.

    Destruction of rat mammary tumor and normal tissue microcirculation by hematoporphyrin derivative photoradiation observed in vivo in sandwich observation chambers

    Cancer Res.

    (1986)
  • Q. Peng et al.

    Distribution and photosensitizing efficiency of porphyrins induced by application of exogenous 5-aminolevulinic acid in mice bearing mammary carcinoma

    Int. J. Cancer

    (1992)
  • C.S. Loh et al.

    Oral versus intravenous administration of 5-aminolaevulinic acid for photodynamic therapy

    Br. J. Cancer

    (1993)
  • Cited by (160)

    View all citing articles on Scopus

    Supported by the Hudson–Webber Foundation and Grants GM08420 and CA 23378 from the National Institutes of Health.

    View full text