Photodynamic therapy (
PDT) is a developing approach to the treatment of solid tumours which requires the combined action of light and a photosensitizing
drug in the presence of adequate levels of molecular
oxygen. We have developed a novel series of
photosensitizers based on
zinc phthalocyanine which are water-soluble and contain neutral (
TDEPC), positive (PPC) and negative (TCPC) side-chains. The
PDT effects of these sensitizers have been studied in a mouse model bearing the RIF-1 murine
fibrosarcoma line studying tumour regrowth delay,
phosphate metabolism by magnetic resonance spectroscopy (MRS) and blood flow, using D2O uptake and MRS. The two main aims of the study were to determine if MRS measurements made at the time of
PDT treatment could potentially be predictive of ultimate
PDT efficacy and to assess the effects of sensitizer charge on
PDT in this model. It was clearly demonstrated that there is a relationship between MRS measurements during and immediately following
PDT and the ultimate effect on the tumour. For all three drugs, tumour regrowth delay was greater with a 1-h time interval between
drug and light administration than with a 24-h interval. In both cases, the order of tumour regrowth delay was PPC >
TDEPC = TCPC (though the data at 24 h were not statistically significant). Correspondingly, there were greater effects on
phosphate metabolism (measured at the time of
PDT or soon after) for the 1-h than for the 24-h time interval. Again effects were greatest with the cationic PPC, with the sequence being PPC >
TDEPC > TCPC. A parallel sequence was observed for the blood flow effects, demonstrating that reduction in blood flow is an important factor in
PDT with these sensitizers.