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Photodynamic Therapy Using a Protoporphyrinogen Oxidase Inhibitor¹

Division of Surgical Oncology, Henry Vogt Cancer Institute, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40292 [V. H. F., T. J. W., K. S. M., P. S. H.]; FMC Corporation, Agricultural Chemical Group, Research and Development, Princeton, New Jersey 08543 [B. P. H., D. A. Y.]; and Department of Pathology and Clinical Laboratories, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115 [J. W. W.]

The use of endogenously created porphyrins as an alternative to photosensitizer injection for photodynamic therapy is a rapidly evolving area of study. One common method to induce porphyrin synthesis and accumulation in cells is the topical, oral, or parenteral administration of 5-aminolevulinic acid, a precursor for heme biosynthesis. Porphyrin accumulation 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 protoporphyrinogen 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, the 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 ppm FP-846 in feed for 3 days and 300 J/cm² 602–670 nm light (23% cure) was similar to the response in animals given 10 mg/kg Photofrin and the same light dose (20%).

¹ This investigation was supported by USPHS Grant CA51771 awarded by the National Cancer Institute, Department of Health and Human Services, by the Department of Surgery, the Henry Vogt Cancer Institute at the James Graham Brown Cancer Center, and FMC Corporation, Agricultural Chemical Group.

² To whom requests for reprints should be addressed, at Division of Surgical Oncology, Henry Vogt Cancer Institute, James Graham Brown Cancer Center, University of Louisville, 529 South Jackson Street, Louisville, KY 40292. Phone: (502) 852-8036; Fax: (502) 852-8031; E-mail: vhfing01@pdt.bcc.louisville.edu.

Received 4/ 9/97. Accepted 8/16/97.