31P 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 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. © 1999 Cancer Research Campaig

Carbogen-induced changes in rat mammary tumour oxygenation reported by near infrared spectroscopy

We have evaluated the ability of steady-state, radially-resolved, broad-band near infrared diffuse reflectance spectroscopy to measure carbogen-induced changes in haemoglobin oxygen saturation (SO2) and total haemoglobin concentration in a rat R3230 mammary adenocarcinoma model in vivo. Detectable shifts toward higher saturations were evident in all tumours (n = 16) immediately after the onset of carbogen breathing. The SO2 reached a new equilibrium within 1 min and remained approximately constant during 200–300 s of administration. The return to baseline saturation was more gradual when carbogen delivery was stopped. The degree to which carbogen increased SO2 was variable among tumours, with a tendency for tumours with lower initial SO2 to exhibit larger changes. Tumour haemoglobin concentrations at the time of peak enhancement were also variable. In the majority of cases, haemoglobin concentration decreased in response to carbogen, indicating that increased tumour blood volume was not responsible for the observed elevation in SO2. We observed no apparent relationship between the extent of the change in tumour haemoglobin concentration and the magnitude of the change in the saturation. Near infrared diffuse reflectance spectroscopy provides a rapid, non-invasive means of monitoring spatially averaged changes in tumour haemoglobin oxygen saturation induced by oxygen modifiers. © 1999 Cancer Research Campaig