The response of human glioma spheroids to ALA-mediated photodynamic therapy subjected to various optical dose delivery schemes is investigated. In particular, the effects of fluence, fluence rate, light dose fractionation and long-term repeat PDT is considered. Improved PDT response was found for low fluence rate photodynamic treatments i.e. those at or below 25 mW cm-2 . Results are consistent with the self-sensitized singlet oxygen mediated photobleaching model of Georgakoudi et al (Georgakoudi, 1998., in which the response is attributed to the deposition of singlet oxygen to a larger volume, i.e., deeper into the spheroid. The efficacy of high-fluence rate PDT (150 mW cm-2) can be improved by the introduction of dark intervals---an approximately 35% enhanced spheroid response was observed with cyclic intervals of between 15 and 45 s. Shorter on/off cycles appear more effective than longer cycles; Repetitive PDT consisting of multiple weekly treatments at sub-optimal fluences (12.5 or 25 J cm-2) revealed marked improvements in efficacy. (Abstract shortened by UMI.)
