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Picket-Fence Porphyrins as Potential Phototherapeutic Agents¹

Departments of Biochemistry [W. J. H., M. K., F. A., S. L. G., R. H.] and of Chemistry [W. J. H., D. C. B., D. G. W.], and the University of Rochester Cancer Center [R. H.], The University of Rochester, School of Medicine and Dentistry, Rochester, New York 14642

The synthetic "picket fence" porphyrin, tetra(o-acetamidophenyl)porphine (TAc), as a biological photosensitizer has been evaluated both in vitro and in vivo in mitochondria from the R3230AC mammary tumor. Studies in vitro, consisting of incubation of mitochondria with TAc at a concentration of 4.0 µg/ml followed by photolysis, result in the inhibition of cytochrome c oxidase, proton translocating ATPase, succinate dehydrogenase, and malate dehydrogenase. The diminution in activity of the first three enzymes is approximately 2-fold greater than that seen with Photofrin II under the same conditions. Although TAc exists as four isolable atropisomers, no differences among these different forms were observed in their photosensitized inhibition of mitochondrial enzymes. Administration to tumor-bearing rats of TAc i.p. at a dose of 25 mg/kg did result in accumulation of porphyrin within the mitochondria of the R3230AC tumor as determined by subsequent irradiation of isolated mitochondria. The potential utility of TAc and related porphyrins in cancer phototherapy is discussed.

¹ Supported by Grant PDT-264, American Cancer Society.

² Supported by USPHS Grant CA 17988, NIH, and the John L. Wilmot Fellowship Fund.

³ To whom requests for reprints should be addressed, at Department of Biochemistry, Box 607, University of Rochester School of Medicine and Densitry, 601 Elmwood Avenue, Rochester, NY 14642.

Received 8/25/87. Revised 11/23/87. Accepted 12/ 1/87.