ALA- and ALA-ester-mediated photodynamic therapy of human glioma spheroids.
The effects of photodynamic therapy (PDT) in human glioma spheroids incubated in 5-aminolevulinic acid (ALA), or ALA esters, are investigated. Spheroid survival and growth are monitored following PDT at representative drug concentrations, light doses, and dose rates. The primary finding of this study is that the response of human glioma spheroids to PDT with lipophilic ester derivatives, such as benzyl-ALA and hexyl-ALA, is equivalent to that observed with ALA, however, this equivalency is obtained for ester concentrations 10-20 times lower than the parent compound. The enhanced efficiency of the esters is likely due to their increased membrane penetrance. Potential clinical advantages of using lipophilic esters in PDT of gliomas are discussed.
Department of Neurosurgery, Rikshospitalet, Oslo, Norway.
Henry
H
Hirschberg
Chung-Ho
CH
Sun
Bruce J
BJ
Tromberg
Steen J
SJ
Madsen
D000622:Aminolevulinic Acid / Q000494:pharmacology*; D001932:Brain Neoplasms; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004952:Esters; D005910:Glioma; D006801:Humans; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D018874:Spheroids, Cellular / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004952:Esters; D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid