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The chick chorioallantoic membrane (CAM) model was used to study vascular effects of photodynamic therapy (PDT) and hyperthermia (HPT) and the synergism of these modalities. The CAM is a convenient medium for monitoring the modifications of the vasculature. It is possible to view the CAM and to examine structural changes of individual blood vessels in real time. Moreover, the CAM is a closed system which lends itself to mathematical modeling of the temporal and spatial temperature profile and in which HPT can be performed quantitatively and to a selected depth, using different lasers. A porphyrin-type photosensitizer solution was applied to areas of the CAM, defined by teflon O-rings placed on the surface. Uptake dynamics of the sensitizer into the CAM was determined by analyzing its fluorescence in vivo. The CAM area was irradiated with a dual-wavelength laser system composed of a dye laser at 644 nm (to induce PDT) and a CO2 laser at 10.6 microns (to bring about HPT). Damage to the CAM vasculature, due to combined PDT+HPT, was compared to the outcome of the separate modalities, and a synergistic effect of about 40% was observed.

The singlet-oxygen-mediated reaction of meso-tetraphenylporphine tetrasulphonate (TPPS4) with different chemical acceptors in buffered aqueous solution was studied as a function of temperature. Imidazole, tryptophan, dimethyl p-nitrosoaniline, (RNO) and furfuryl alcohol served as acceptors. The measurements were performed in real time by spectroscopic or electrochemical monitoring of the consumption of the various reagents, acceptors or dissolved oxygen as a function of the absorbed energy. The results show the following increases in the reaction rate over the temperature range 15-45 degrees C: tryptophan (86%), RNO (90%), furfuryl alcohol (150%) and imidazole (210%). The influence of temperature-correlated changes in the initial oxygen concentration and pH was investigated. Possible implications of the present results for the synergistic influence of hyperthermia and photodynamic therapy are discussed.