Two course illuminating scheme improves aminolevulinic acid photodynamic therapy in cell cultures.
Photodynamic therapy with the pro-drug 5-aminolaevulinic acid (ALA-PDT) is being used for the treatment of Barrett's oesophagus. We postulated that a first early course of ALA-PDT would increase protoporphyrin IX (PPIX) accumulation and thus the efficacy of a second course of ALA-PDT, by manipulating ferrochelatase (FC) and porphobilinogen deaminase (PBG-d) activity. Human EBV-transformed lymphoblastoid cells were used as a model of human tumour cells for the ability to form haem is present in all cells. After a single course of illumination (633 nm, 100 mW/cm2) the FC activity decreased significantly whereas the PBG-d activity did not change. During continued incubation with ALA following the first illumination, cells accumulated up to four times more PPIX than non-illuminated controls [220% +/- 30% versus (vs) 55% +/- 5%; p<0.001]. Two illuminations resulted in more cell death than one illumination (97% +/- 1% vs 80% +/- 2%; p<0.001). Since a second course of ALA-PDT within 3 hr after the first course resulted in a four fold increase in PPIX accumulation and significantly more cell death, we propose that a two course ALA-PDT scheme might improve the efficacy of this treatment for Barrett's oesophagus.
Hinnen
P
P
Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
Siersema
P D
PD
Edixhoven
A
A
Wilson
J H P
JH
de Rooij
F W M
FW
D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D001471:Barrett Esophagus / Q000628:therapy; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D005294:Ferrochelatase / Q000096:biosynthesis; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000096:biosynthesis; D008027:Light; D010778:Photochemotherapy / Q000379:methods*; D011166:Porphyrins / Q000378:metabolism; D011524:Protoporphyrins / Q000096:biosynthesis; D013997:Time Factors
D011166:Porphyrins; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D011163:Hydroxymethylbilane Synthase; D005294:Ferrochelatase