Timing of illumination is essential for effective and safe photodynamic therapy: a study in the normal rat oesophagus

5-Aminolaevulinic acid (ALA)-induced, protoporphyrin IX (PpIX)-mediated photodynamic therapy (PDT) is an experimental treatment modality for (pre)malignant oesophageal lesions. This study aimed to optimize the time of illumination after ALA administration. Six groups of eight rats received 200 mg kg...

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Bibliographic Details
Published in:British journal of cancer 1999-02, Vol.79 (5-6), p.825-830
Main Authors: VAN DEN BOOGERT, J, VAN HILLEGERSBERG, R, VAN STAVEREN, H. J, DE BRUIN, R. W. F, VAN DEKKEN, H, SIERSEMA, P. D, TILANUS, H. W
Format: Article
Language:English
Subjects:
Aminolevulinic Acid - toxicity
Animals
Biological and medical sciences
Edema
Esophagus - drug effects
Esophagus - pathology
Esophagus - radiation effects
Light - adverse effects
Male
Medical sciences
Mucous Membrane - drug effects
Mucous Membrane - pathology
Mucous Membrane - radiation effects
Muscle, Smooth - drug effects
Muscle, Smooth - pathology
Muscle, Smooth - radiation effects
Photochemotherapy - adverse effects
Photochemotherapy - methods
Photoradiation therapy and photosensitizing agent
Photosensitizing Agents - toxicity
Protoporphyrins - toxicity
Rats
Rats, Wistar
Regular
Spectrometry, Fluorescence
Time Factors
Treatment with physical agents
Treatment. General aspects
Tumors
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Summary:5-Aminolaevulinic acid (ALA)-induced, protoporphyrin IX (PpIX)-mediated photodynamic therapy (PDT) is an experimental treatment modality for (pre)malignant oesophageal lesions. This study aimed to optimize the time of illumination after ALA administration. Six groups of eight rats received 200 mg kg(-1) ALA orally, eight rats served as controls. Illumination was performed at 1, 2, 3, 4, 6 or 12 h after ALA administration with a 1-cm cylindrical diffuser placed in a balloon catheter (laser parameters: 633 nm, 25 J radiant energy, power output 100 mW). During illumination, fluorescence measurements and light dosimetry were performed. Animals were sacrificed at 48 h (n = 4) or 28 days (n = 4) after PDT. At day 28, an oesophagogram was performed. Largest PpIX fluorescence was found at 3 h after ALA administration. In vivo fluence rate was three times higher than the calculated incident fluence rate. At 48 h after PDT, major epithelial damage was found in all animals illuminated at 2 h, whereas less epithelial damage was found at 3-6 h and none at 1 and 12 h. In animals illuminated at 4, 6 and 12 h, but not at 2 h, oesophagograms showed severe dilatations and histology showed loss of Schwann cells. These results demonstrate that the choice of time interval between ALA administration and illumination is critical for achieving epithelial damage without oesophageal functional impairment. A short interval of 2-3 h seems to be most appropriate.
ISSN:0007-0920
1532-1827
DOI:10.1038/sj.bjc.6690132