The effects of fluence rate are investigated in human glioma spheroids incubated in 5-aminolevulinic acid (ALA). It is shown that the response of glioma spheroids to ALA-mediated PDT depends strongly on the rate at which the light dose is delivered. At low doses, lower fluence rates are more effective. For example, at a dose of 50 J/cm2, near total spheroid kill is observed at fluence rates of as low as 10 mW/cm2. Below 10 mW/cm2, however, treatments are not as effective. The fluence rate effect is not as pronounced at higher doses where a favorable response is observed throughout the range of fluence rates investigated. The clinical implications of these findings are discussed.

Although 5-aminolevulinic acid (ALA) has several advantages over other photosensitizers, its hydrophilic nature gives rise to relatively poor transport across cell membranes. Esterification of ALA is a commonly used strategy to improve the effectiveness of ALA. In this study, the effectiveness of photodynamic therapy (PDT) in human glioma spheroids incubated in ALA, or ALA esters, is investigated. Spheroid survival and growth are monitored following PDT at representative drug concentrations and light fluences. It is shown 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 observed for ester concentrations 10 to 20 times lower than the parent compound.