Routine experimental system for defining conditions used in photodynamic therapy and fluorescence photodetection of (non-) neoplastic epithelia

A common method to induce enhanced short-term endogenous porphyrin synthesi s and accumulation in cell is the topical, systemic application of 5-aminol evulinic acid or one of its derivatives. This circumvents the intravenous a dministration of photosensitizers normally used for photodynamic therapy (P DT) of fluorescence photodetection. However, in the majority of potential m edical indications, optimal conditions with respect to the porphyrin precur sor or its pharmaceutical formulation have not yet been found. Due to ethic al restrictions and animal right directives, the number of available test o bjects is limited. Hence, definition and use of nonanimal test methods are needed. Tissue and organ cultures are a promising approach in replacing cos t intensive animal models in early stages of drug development. In this pape r, we present a tissue culture, which can among others be used routinely to answer specific questions emerging in the field of photodynamic therapy an d fluorescence photodetection. This technique uses mucosae excised from she ep paranasal sinuses or pig bladder, which is cultured under controlled con ditions. It allows quasiquantitative testing of different protoporphyrin IX precursors with respect to dose-response curves and pharmacokinetics, as w ell as the evaluation of different incubation conditions and/or different d rug formulations. Furthermore, this approach, when combined with the use of electron microscopy and fluorescence-based methods, can be used to quantit atively determine the therapeutic outcome following protoporphyrin IX-media ted PDT. (C) 2001 Society or Photo-Optical Instrumentation Engineers.