Biodistribution and phototoxicity of 5-aminolevulinic acid-induced PpIX in an orthotopic rat bladder tumor model.
5-Aminolevulinic acid (ALA) is a precursor of heme biosynthesis. In the penultimate step of this biosynthesis, protoporphyrin IX (PpIX), an effective photosensitizer, is generated. In this study, the biodistribution and photodynamic effect of ALA-induced PpIX were investigated in an orthotopic rat bladder tumor model. A quantitative comparison of PpIX biodistribution by extraction and fluorescence spectroscopy following intravenous and intravesical administration of ALA was made. The tumor to normal bladder wall ratio was 2:1 at 4 hours for both delivery modes. Fluorescence microscopy demonstrated predominantly cellular rather than stromal PpIX fluorescence. Phototoxicity, evaluated 4 hours after ALA administration, was light dose-dependent with the most efficient tumor necrosis being observed upon 150 J/cm.2 of 630 nm. irradiation. These data suggest that optimized photodynamic therapy with ALA-induced PpIX may be an alternative treatment for superficial bladder carcinoma.
Iinuma
S
S
Wellman Laboratories of Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston.
Bachor
R
R
Flotte
T
T
Hasan
T
T
D000622:Aminolevulinic Acid / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D005260:Female; D009368:Neoplasm Transplantation; D010778:Photochemotherapy; D011524:Protoporphyrins / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX