HETEROGENEOUS TUMOR RESPONSE TO PHOTODYNAMIC THERAPY ASSESSED BY INVIVO LOCALIZED P-31 NMR-SPECTROSCOPY

Photodynamic therapy (PDT) is efficacious in the treatment of small malignant lesions when all cells in the tumour receive sufficient drug, oxygen and light to induce a photodynamic effect capable of complete cytotoxicity. In large tumours, only partial effectiveness is observed presumably because of insufficient light penetration into the tissue. The heterogeneity of the metabolic response in mammary tumours following PDT has been followed in vivo using localised phosphorus NMR spectroscopy. Alterations in nucleoside triphosphates (NTP), inorganic phosphate (P(i)) and pH within localised regions of the tumour were monitored over 24-48 h following PDT irradiation of the tumour. Reduction of NTP and increases in P(i) were observed at 4-6 h after PDT irradiation in all regions of treated tumours. The uppermost regions of the tumours (those nearest the skin surface and exposed to the greatest light fluence) displayed the greatest and most prolonged reduction of NTP and concomitant increase in P(i) resulting in necrosis. The metabolite concentrations in tumour regions located towards the base of the tumour returned to near pre-treatment levels by 24-48 h after irradiation. The ability to follow heterogeneous metabolic responses in situ provides one means to assess the degree of metabolic inhibition which subsequently leads to tumour necrosis.