PHOTODYNAMIC EFFECTS INDUCED BY MESO-TETRAKIS[4(CARBOXYMETHYLENEOXY)PHENYL] PORPHYRIN USING RAT HEPATIC MICROSOMES AS MODEL MEMBRANES

Porphyrins, in combination with light, offer an alternate approach to the treatment of cancer, in the form of photodynamic therapy (PDT). Wi th a view to locate new porphyrins for use in PDT, we evaluated the ab ility of a novel water-soluble porphyrin, o-tetrakis[4-(carboxymethyle neoxy)phenyl]porphyrin (T4CPP) to induce photodamage in membranes, usi ng rat hepatic microsomes as a model system. Hepatic microsomes treate d with T4CPP and exposed to visible light showed significant lipid per oxidation, as assessed by the formation of conjugated dienes, lipid hy droperoxides, and thiobarbituric acid-reactive substances. The peroxid ation induced was both time- and concentration-dependent. T4CPP plus l ight also resulted in the destruction of the microsomal enzymes adenos ine triphosphatase and glucose-6-phosphatase. Analysis of the products of peroxidation and selective inhibition by specific inhibitors showe d that the oxidative damage induced was mainly due to singlet oxygen a nd partly due to hydroxyl radical. The porphyrin T4CPP was efficiently labeled with Tc-99m. When this Tc-99m-labeled porphyrin was injected into a mammary-tumor-bearing rat, it accumulated in the tumor. Our stu dies suggest that T4CPP, due to its potential to localize in tumors an d to induce membrane damage as exemplified by alteration in rat liver microsomes, may have possible applications in this new modality of can cer treatment. (C) 1997 Academic Press.