PHOTODYNAMIC THERAPY USING A PROTOPORPHYRINOGEN OXIDASE INHIBITOR

The use of endogenously created porphyrins as an alternative to photos ensitizer injection for photodynamic therapy is a rapidly evolving are a of study, One common method to induce porphyrin synthesis and accumu lation in cells is the topical, oral, or parenteral administration of 5-aminolevulinic acid, a precursor for heme biosynthesis, Porphyrin ac cumulation may also be elicited by the use of enzyme inhibitors of the heme biosynthetic pathway, Groups of DBA/2 mice bearing SMT-F mammary tumors were placed on a diet containing 0-4000 ppm of a proto-porphyr inogen oxidase inhibitor, FP-846. This agent blocks a critical step in porphyrin metabolism and results in elevated intracellular levels of protoporphyrin IX, Light treatment of tumors produced both initial and long-term regression that was dependent on the amount of inhibitor, t he duration of inhibitor exposure to animals, and the amount of light used in PDT, Tumor regression occurred without significant destruction of normal tissues in the treatment field and without initial vascular constriction or blood flow stasis, Tumor cure in animals given 4000 p pm FP-846 in feed for 3 days and 300 J/cm(2) 602-670 nm light (23% cur e) was similar to the response in animals given 10 mg/kg Photofrin and the same light dose (20%).