P-31 magnetic resonance spectroscopy as a predictor of efficacy in photodynamic therapy using differently charged zinc phthalocyanines

Photodynamic therapy (PDT) is a developing approach to the treatment of sol id tumours which requires the combined action of light and a photosensitizi ng drug in the presence of adequate levels of molecular oxygen. We have dev eloped a novel series of photosensitizers based on zinc phthalocyanine whic h are water-soluble and contain neutral (TDEPC), positive (PPC) and negativ e (TCPC) side-chains. The PDT effects of these sensitizers have been studie d in a mouse model bearing the RIF-1 murine fibrosarcoma line studying tumo ur regrowth delay, phosphate metabolism by magnetic resonance spectroscopy (MRS) and blood flow, using D2O uptake and MRS. The two main aims of the st udy were to determine ii 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 demonstr ated that there is a relationship between MRS measurements during and immed iately following PDT and the ultimate effect on the tumour. For all three d rugs, tumour regrowth delay was greater with a 1-h time interval between dr ug and light administration than with a 24-h interval. In both cases, the o rder 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 parall el sequence was observed for the blood flow effects, demonstrating that red uction in blood flow is an important factor in PDT with these sensitizers. (C) 1999 Cancer Research Campaign.