Quantitative intracellular oxygen availability before and after 5-aminolevulinic acid skin photodynamic therapy

Abstract

BackgroundDuring photodynamic therapy (PDT) oxygen is transformed into reactive oxygen species (ROS) to induce cellular apoptosis in (pre)malignant cells. Real time oxygen availability measurement is clinically available with the Cellular Oxygen Metabolism (COMET) monitor. MethodsPrimary objective is to show that mitochondrial oxygen availability (mitoPO2) measurement is possible during clinical ALA-PDT. The secondary aim was to determine the pain sensation, because it is the most commonly reported side effect of PDT. Before and after the two fraction PDT treatment, with a 2-hour dark period, mitoPO2 was measured and reported pain was documented with a visual analog scale (VAS) 0–100. ResultsNine patients were included. Before the first PDT session the median signal quality was [IQR] 55.0% [34.2–68.0], which decreased after session one to 0% [0.0–10.0]. MitoPO2 was 40.0 [17.7–53.8] mmHg and increased afterwards to 61.8 [38.2–64.8] mmHg. This likely the result of the delay time between the illumination stop and the mitoPO2 measurements in a vasodilated, visibly red lesion.Before session two signal quality was 10.4% [0–20.15], 40% lower than at the start. In 5 patients the signal quality after session 2 was too low because of photobleaching and insufficient regeneration of PpIX, median 0% [0–10]. Subjects reported low median VAS scores, all below 3, directly after the mitoPO2 measurements. ConclusionWith COMET we were able to reliably measure mitochondrial oxygen concentrations during photodynamic therapy. Signal quality drastically decreases after a PDT session because of PpIX deterioration during the illumination phase.