EARLY BIOCHEMICAL RESPONSES TO PHOTODYNAMIC THERAPY MONITORED BY NMR SPECTROSCOPY

Abstract

Abstract Studies directed at determining the biochemical events that lead to tumor cytotoxicity following photodynamic therapy, a promising new approach for treatment of neoplasia, have demonstrated that exposure of R3230AC mammary tumors to hematoporphyrin derivative or Photofrin II plus visible light caused marked impairment of mitochondrial enzymes functioning in oxidative phosphorylation and electron transport. 31 P‐NMR spectroscopy has now demonstrated that a rapid and striking decrease in NTP (ATP) levels, concomitant with a marked increase in P ; , occurs in tumors shortly after photodynamic therapy. These effects appear to be fluence related. Possible changes in tumor vascularity, as detected by 2 H‐NMR measurements of the uptake of D 2 0, were not observed under the conditions studied. Taken together with our earlier results, we conclude that the reduction in tumor ATP levels in situ , probably via inhibition of mitochondrial function, is a direct and early response of neoplastic tissue to porphyrin‐induced photosensitization.