Heterogeneity of 6-aminolevulinic acid-induced protoporphyrin IX fluorescence in human glioma cells and leukemic lymphocytes

Abstract Delta-aminolevulinic acid (ALA)-PDT efficacy is particularly dependent on the quality of protoporphyrin IX (PplX)-induced synthesis. The purpose of this study was to determine the ability of cells from two human cancer types to synthesise PplX after ALA administration. Biopsies of glioma cells have been obtained from patients with glioblastomas that have or have not been given ALA IV (ex vivo incubation). Peripheral blood lymphocytes, obtained from leukemic patients, have also been ALA-incubated in vitro. In glioma cells, fluorescence heterogeneity was extensive either in ALA infused patients or in ex vivo ALA incubated cells. Mean intensities after 3 h were 1 lOcts (range 0-340) and WOOcts (range 0-3600). Similar results were found in leukemic lymphocytes where cell fluorescence varied from 0 to 480 cts with a percentage of fluorescent cells varying with time and from one patient to another. Furthermore, PplX was not detectable in two patients with CLL. These observations suggest that a marked heterogeneity of ALA uptake and/or PplX synthesis exists in a given human cancer cell population particularly after systemic administration. Improvements for ALA transformation into PplX are strongly recommended to ensure the efficacy of ALA/ PpIX-PDT. [Neurol Res 2000; 22: 361-368]