Multicell tumor spheroids in photodynamic therapy

Background and Objectives: Multicell spheroids (MCSs) represent a simple in vitro system ideally suited for studying the effects of a wide variety of investigational treatments including photodynamic therapy (PDT). Study Design/Materials and Methods: In the first section of this review study, an overview of the current literature on MCS in PDT will be presented. Knowledge of basic PDT parameters has been gained from numerous MCS studies, in particular, the mechanisms of sensitizer photobleaching have been elucidated. MCSs have also proven useful for the study of complex PDT treatment regimens including multiple treatments and combined therapies involving PDT and ionizing radiation or hyperthermia. The purpose of the second part of this review is to present results from recent studies in our laboratory aimed at developing MCS models suitable for investigating tumor cell invasion and angiogenesis-processes characteristic of high-grade gliomas. Results and Conclusion: To that end, progress has recently been made to develop a more accurate in vivo brain tumor model consisting of biopsy-derived human tumor spheroids implanted into the brains of immunodeficient rats. Finally, recent work suggests that computer simulations may prove useful to describe the growth of MCS and predict the effects of investigational therapies including PDT. Such in silico models have made a number of counterintuitive predictions that have been verified in vitro and, as such, could guide the development of improved therapeutics.