Oedema formation in experimental photo-irradiation therapy of brain tumours using 5-ALA.
BACKGROUND
Five-aminolevulinic acid (5-ALA) induces the specific accumulation of photosensitising porphyrins in malignant gliomas and has been explored for photo-irradiation therapy of these tumours. However, information is unavailable on whether and to what extent this treatment modality may induce the formation of brain oedema, and how potential oedema might be treated.


METHODS
Rats were implanted with C6 gliomas. Eight days later magnetic resonance images (MRI) were obtained. On day 9 rats received 100 mg 5-ALA/kg b.w. and were craniotomized for photo-irradiation of tumours 6 hours later (100 J/cm2, 635 nm argon-dye laser). Part of the animals was treated with daily dexamethasone injections (0.3 mg/kg), beginning 6 hours before phototherapy. 72 hours later, brains were removed and dissected according to tumour dimensions on pre-therapy MRI into "tumour", "brain around tumour" (BAT), residual cortex and basal ganglia, for measurements of water contents. Measurements were also performed in untreated animals with tumours, with or without steroid treatment and in control animals. An additional group of animals lacking tumours, with or without steroid treatment, underwent 5-ALA-phototherapy to determine effects on normal brain.


RESULTS
C6 gliomas induced brain oedema, which responded to steroid treatment. 5-ALA-phototherapy resulted in additional oedema, which responded partly to steroids. 5-ALA-phototherapy of normal brain increased water content moderately in irradiated cortex. This oedema was also partly counteracted by steroids.


CONCLUSIONS
Photo-irradiation therapy with 5-ALA induces oedema which is partly counteracted by steroid therapy. The possibility of steroid resistant oedema formation should be considered when planning human trials with this treatment modality.
Ito
S
S
Department of Neurosurgery, Chiba University, Japan.
Rachinger
W
W
Stepp
H
H
Reulen
H J
HJ
Stummer
W
W
D000622:Aminolevulinic Acid / Q000009:adverse effects*; D000818:Animals; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology*; D001932:Brain Neoplasms / Q000188:drug therapy*; D003907:Dexamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D005910:Glioma / Q000188:drug therapy*; D005938:Glucocorticoids / Q000627:therapeutic use; D008297:Male; D010778:Photochemotherapy / Q000009:adverse effects*; D017319:Photosensitizing Agents / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar
D005938:Glucocorticoids; D017319:Photosensitizing Agents; D003907:Dexamethasone; D000622:Aminolevulinic Acid