Development of a novel indwelling balloon applicator for optimizing light delivery in photodynamic therapy

Background and Objective: A human glioma spheroid model is used to investigate the efficacy of different light delivery schemes in 5-aminolevulinic acid (ALA)mediated photodynamic therapy (PDT). The results provide the rationale for the development of an indwelling balloon applicator for optimizing light delivery. Study Design/Materials and Methods: Human glioma spheroids were incubated in ALA (100 or 1000 mug ml(-1)) for 4 hours and subjected to various light irradiation schemes. In one set of experiments, spheroid survival was monitored as a function of light fluence rate (5-200 mW cm(-2)). In all cases, spheroids were exposed to fluences of either 25 or 50 J cm(-2). In a second study, the effects of repeated weekly PDT treatments. using sub-threshold fluences, were investigated. One group of spheroids was subjected to three treatments using fluences of 12, 12, and 25 J cm(-2). Results were compared to spheroids receiving single treatments of either 12 or 25 J cm(-2). A fluence rate of 25 mW cm(-2) was used for all three groups of spheroids. In all cases, the effect of a given irradiation scheme was evaluated by monitoring spheroid growth. Results: Low fluence rates produce greater cell kill than high fluence rates. The minimum effective fluence rate in human glioma spheroids is approximately 10 mW cm(-2). Repeated weekly PDT treatments with sub-threshold fluences result in significant cell kill. In spheroids surviving the PDT treatments, growth is suppressed for the duration of the treatment period. Conclusion: The results of the in vitro studies support the development of an indwelling balloon applicator for the delivery of light doses in long term multi-fractionated PDT regimens. Lasers Surg. Med. 29:406-412, 2001. (C) 2001 Wiley-Liss, Inc.