LIGHT-DEPENDENT OXYGEN-CONSUMPTION IN BACTERIOCHLOROPHYLL-SERINE-TREATED MELANOMA TUMORS - ONLINE DETERMINATION USING A TISSUE-INSERTED OXYGEN MICROSENSOR

Successful application of anticancer therapy, and especially photodyna mic therapy (PDT) mediated by type II (PDTII) processes, depends on th e oxygen content within the tumor before, during and after treatment. The high consumption of oxygen during type II PDT imposes constraints on therapy strategies. Although rates of oxygen consumption and replet ion during PDTII were suggested by theoretical studies, direct measure ments have not been reported, Application of a novel oxygen sensor all owed continuous and direct in situ measurements (up to a depth of 8-9 mm from the tumor surface and for several hours) of temporal variation s in the oxygen partial pressure (pO(2)) during PDT. Highly pigmented M2R mouse melanoma tumors implanted in CD1 nude mice were treated with bacteriochlorophyll-serine (Bchl-Ser; a new photodynamic reagent) and were subjected to fractionated illumination (700 < lambda < 900 nm) a t a fluence rate of 12 mW cm(-2). This illumination led to total oxyge n depletion with an average consumption rate of 7.2 mu M(O-2) s(-1). S pontaneous reoxygenation (at an average rate of 2.5 mu M(O-2)/s) was o bserved during the following dark period. These rates are in good agre ement with theoretical considerations (Foster et al., Radiat. Res. 126 , 296, 1991 and Henning et al., Radiat. Res. 142, 221, 1995). The obse rved patterns of oxygen consumption and recovery during prolonged peri ods of light/dark cycles were interpreted in terms of vasculature dama ge and sensitizer clearance. The presented data support the previously suggested advantages of fractionated illumination for type II photody namic processes.