Predicting efficacy of photodynamic therapy by real-time FDG-PET in a mouse tumour model

Dynamic positron emission tomography (PET) combined with the constant infusion of 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) as a tracer permits real-time monitoring of systemic transient metabolic changes resulting from photodynamic therapy (PDT) in tumour bearing animals. The effect of PDT on tumour FDG uptake rates was evaluated using four different sulfonated phthalocyanine analogs as photosensitizers (PS) in combination with either continuous or fractionated illumination protocols. Mice bearing two EMT-6 tumours were infused with FDG to start PDT 30 min later. Dynamic images were acquired to produce FDG uptake over time for the treated and reference tumours. Practically all PDT protocols induced a reduction in the FDG uptake rates in the treated tumour during PDT, except for the zinc tetrasulfophthalocyanine, when using fractionated light, reflecting the low photodynamic efficacy of this PS. In general, the response to PDT was characterized by a rebound in the FDG uptake rate after illumination. A strong drop in FDG tumour uptake rates during PDT, followed by a strong rebound, together with short delay-to-response times, corresponded to optimal long-term tumour response outcomes. This dynamic FDG-PET protocol provides real-time observations to predict long-term PDT efficacy, while using fewer animals than conventional methods, thus making possible the rapid optimization of treatment parameters.