Photodynamic therapy of human glioma spheroids using 5-aminolevulinic acid

The response of human glioma spheroids to 5-aminole-vulinic acid (ALA)-medi ated photodynamic therapy (PDT) is investigated. A two-photon fluorescence microscopy technique is used to show that human glioma cells readily conver t ALA to protoporphyrin IX throughout the entire spheroid volume. The centr al finding of this study is that the response of human glioma spheroids to ALA-mediated PDT depends not only on the total fluence, but also on the rat e at which the fluence is delivered. At low fluences (less than or equal to 50 J cm(-2)), lower fluence rates are more effective. At a fluence of 50 J cm(-2), near-total spheroid kill is observed at fluence rates of as low as 10 mW cm(-2). The fluence rate effect is not as pronounced at higher fluen ces (>50 J cm(-2)), where a favorable response is observed throughout the r ange of fluence rates investigated, The clinical implications of these find ings are discussed.