Light‐dependent Oxygen Consumption in Bacteriochlorophyll‐Serine‐treated Melanoma Tumors: On‐line Determination Using a Tissue‐inserted Oxygen Microsensor

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Abstract
Successful application of anticancer therapy, and especially photodynamic therapy (PDT) mediated by type II (PDTII) processes, depends on the 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 repletion during PDTII were suggested by theoretical studies, direct measurements have not been reported. Application of a novel oxygen sensor allowed continuous and direct in situ measurements (up to a depth of 8-9 mm from the tumor surface and for several hours) of temporal variations in the oxygen partial pressure (pO2) 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) at a fluence rate of 12 mW cm-2. This illumination led to total oxygen depletion with an average consumption rate of 7.2 microM(O2) s-1. Spontaneous reoxygenation (at an average rate of 2.5 microM(O2)/s) was observed during the following dark period. These rates are in good agreement with theoretical considerations (Foster et al., Radiat. Res. 126, 296, 1991 and Henning et al., Radiat. Res. 142, 221, 1995). The observed patterns of oxygen consumption and recovery during prolonged periods of light/dark cycles were interpreted in terms of vasculature damage and sensitizer clearance. The presented data support the previously suggested advantages of fractionated illumination for type II photodynamic processes.