This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Barber, D. C. Articles by Whitten, D. G. Search for Related Content PubMed PubMed Citation Articles by Barber, D. C. Articles by Whitten, D. G.

Photosensitizing Activities of Picket Fence Porphyrins in Vitro and in Vivo¹

Department of Chemistry, University of Rochester [D. C. B., D. G. W.], Department of Biochemistry, University of Rochester School of Medicine and Dentistry [K. R. V., S. L. G., R. H.], and the University of Rochester Cancer Center [R. H.], Rochester, New York 14642

A set of structurally distinct o-substituted tetraphenylporphyrins, the picket fence porphyrins, were evaluated for their ability to photosensitize tumor mitochondria in vitro, in vivo-in vitro, and tumor implants in situ. Differential photosensitized inactivation efficiencies toward mitochondrial enzymes in vitro are reported for the 12 compounds studied as a function of side chain length and isomer structure. Fluorescence studies in aqueous solution coupled with mitochondrial uptake studies indicate that the observed range of inactivation efficiencies are due to different inherent solubilization properties for the picket fence porphyrins. Studies with the most soluble compound, 3,1-meso-tetrakis(o-propionamidophenyl)porphyrin, using an in vivo-in vitro protocol indicate that a more effective photosensitization can be obtained by using an interval of 4 h between photosensitizer administration and irradiation as compared to 24 h for Photofrin II. Irradiation of tumors in vivo 4 h following administration of 3,1-meso-tetrakis(o-propionamidophenyl)porphyrin, resulted in a mean tumor doubling time more than eight times longer than that observed for untreated tumors. ³¹P NMR spectroscopy in situ indicated that photodynamic therapy using 3,1-meso-tetrakis(o-propionamidophenyl)porphyrin induced a rapid and significant reduction in high energy phosphate metabolites.

¹ Supported by USPHS Grants CA48961 and CA36856, National Institutes of Health.

² To whom requests for reprints should be addressed, at the Department of Biochemistry, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642.

Received 9/28/90. Accepted 1/17/91.