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Selective in Vivo Tumor Localization of Uroporphyrin Isomer I in Mouse Mammary Carcinoma: Superiority over Other Porphyrins in a Comparative Study¹

Department of Internal Medicine, Division of Gastroenterology, University of California, Davis, School of Medicine, Sacramento, California 95817

Twenty-eight porphyrins were evaluated for tumor localization as delineated by fluorescence using a transplantable KHJJ mammary carcinoma in BALB/c mice as the tumor model. Five of the 28 porphyrins were found to localize and of these, one, i.e., uroporphyrin I (UROP I), showed a higher tumor:skin ratio than any of the others; moreover, as no measurable UROP I was present in the gut, the tumor:intestinal porphyrin ratio under the conditions of assay was infinity. Because hematoporphyrin derivative (HPD), a complex mixture of porphyrins has been studied extensively as a tumor localizer, we compared HPD with UROP I at differing doses (2–40 mg/kg) and at different times (3–96 h) following i.v. administration. Dose response curves showed tissue levels of porphyrin to plateau out at doses above 20 mg/kg. Peak tumor HPD and UROP I levels attained 6–18 h after i.v. administration (40 mg porphyrin/kg) were comparable, but tumor retention of HPD over the ensuing 96 h was higher. The ratio of UROP I in tumor compared to skin was significantly greater throughout the period of observation. At all times, no UROP I was detectable in gastrointestinal mucosa. At differing doses (10–40 mg/kg), the tumor:skin ratio for HPD ranged from 1.47–1.85, and for UROP I from 6.06–12.33. As a function of time (6–72 h), the tumor:skin ratios respectively were 1.03–2.38, and 11.9 to infinity. At all times, the tumor:colon mucosa ratio at different doses for HPD approached 1 and for UROP I was infinity. We conclude that the greater specificity of tumor uptake by UROP I and its lack of retention by gut mucosa warrants further study to determine its potential clinical application as a diagnostic marker, particularly for early mucosal cancer, and in photoradiation therapy.

¹ This work has been supported by generous grants in part from the Elsa U. Pardee Foundation, University of California Cancer Research Coordinating Committee, and the Fulbright Commission.

² Visiting Senior Fulbright Scholar from the Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, Egypt.

³ To whom requests for reprints should be addressed.

Received 9/ 9/85. Revised 3/ 4/86. Revised 5/ 6/86. Accepted 6/ 4/86.