Dose-Dependent Metabolic Response of Mammary Carcinoma to Photodynamic Therapy

The metabolic response of mammary carcinoma in the C3H mouse to photodynamic therapy (PDT) was measured using in vivo³¹ P nuclear magnetic resonance (³¹ P- NMR) spectroscopy and pH microelectrodes. Twenty-four hours after administration of Photofrin II (12.5 mg/kg), the tumor was subjected to photoactivation using an argon dye laser. Optical treatment doses were 200, 400, and <tex-math>$600\ {\rm J}/{\rm cm}^{2}$</tex-math> and corresponded to the following tumor control doses: <tex-math>${\rm TCD}_{10/30},\ {\rm TCD}_{50/30}$</tex-math>, and <tex-math>${\rm TCD}_{90/30}$</tex-math>, respectively. In vivo³¹ P- NMR spectra and pH microelectrode measurements were obtained prior to treatment and at 4, 24, 48, and 72 h and 1 week post-treatment. The data revealed a significant (P < 0.0002) alkalosis as indicated by the pH measured by NMR compared to pH measured by microelectrodes at all treatment levels and time points. Spectral differences between treatment groups were apparent as early as 4 h after treatment. The ratio of β-nucleoside triphosphate to inorganic phosphate at 4 h after treatment was significantly (P < 0.01) smaller for <tex-math>$600\ {\rm J}/{\rm cm}^{2}$</tex-math> treatment than for <tex-math>$200\ {\rm J}/{\rm cm}^{2}$</tex-math> treatment. At curative (<tex-math>$600\ {\rm J}/{\rm cm}^{2}$</tex-math>) levels, from 48 h on, no phosphate resonances were detected in the spectra. The pH measured by NMR transiently decreased from pretreatment levels after 200 and <tex-math>$400\ {\rm J}/{\rm cm}^{2}$</tex-math> treatment (P < 0.002, P < 0.009, respectively), while no change in pH from pretreatment values was found after <tex-math>$600\ {\rm J}/{\rm cm}^{2}$</tex-math> treatment. The data suggest that the early metabolic response of mammary carcinoma to PDT, as indicated by³¹ P- NMR spectroscopy, is dose dependent, and may be a sensitive indicator of biological outcome to treatment.