BACKGROUND/OBJECTIVES: Correlation of photodynamic activity (PDT) and fluorescence signaling for free and pegylated meta-tetrahydroxyphenylchlorin (mTHPC) in nude mice with mesothelioma xenografts. STUDY DESIGN/MATERIALS AND METHODS: Twelve animals received light delivery (20 J/cm(2), 150 mW/cm(2), spot size 1.2 cm) on the tumor and the hind leg 3 days after sensitization with 0.15 mg/kg free mTHPC (n = 6) or equimolar-dosed pegylated mTHPC (n = 6). Groups of three animals each were sensitized with 0.15 and 0.5 mg/kg free mTHPC or equimolar dosed pegylated mTHPC followed after 3 days by fluorescence microscopy measurements. RESULTS: Pegylated mTHPC resulted in a similar extent of PDT-related tumor necrosis but in lower skin phototoxicity than free mTHPC. Both mTHPC formulations were heterogeneously distributed in the tumor and were mainly localized in perivascular areas. Pegylated mTHPC revealed a higher tumor to skin fluorescence intensity ratio than free mTHPC (P<0.001). CONCLUSIONS: Fluorescence signaling measurement has the potential to predict the photodynamic activity for both mTHPC formulations in mesothelioma xenografts