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Effectiveness of a Lysyl Chlorin p6/Chlorin p6 Mixture in Photodynamic Therapy of the Subcutaneous 9L Glioma in the Rat¹

Schools of Veterinary Medicine [M. W. L., R. J. H.] and Medicine [J. E. B., S. A.] and Department of Chemistry [S-J. L., K. M. S.], University of California, Davis, California 95616

A new photosensitizer, LCP, a combination of lysyl chlorin p6 and chlorin p6, was synthesized and tested for effectiveness in photodynamic therapy using s.c. implanted 9L glioma tumors in rats. Tumors were irradiated with 664-nm light 4 h after LCP injection. Mean intratumoral temperature elevations were less than 4°C using a power density of 50 mW/cm² for 33.3 min (100 J/cm²). Subsequent experiments examining histological changes and tumor regrowth used a power density of 50 mW/cm² and total energy densities of 25, 50, and 100 J/cm². Microscopically, an energy density-dependent coagulation necrosis of tumor cells occurred in treated tumors. Long term inhibition of tumor growth was achieved only at an energy density of 100 J/cm². Side effects of treatment were seen only in the irradiated area and consisted of coagulation necrosis of normal tissues in rats treated at 50 and 100 J/cm², including severe skin necrosis. Exposure of rats to fluorescent room light did not cause any macroscopically detectable skin damage. Our data indicate that photodynamic destruction of s.c. 9L glioma tumors using LCP as a photosensitizer results in significant tumor growth inhibition and that further study of LCP is warranted.

¹ Part of this research was supported by the NIH (K. M. S.: CA 52997) and by a National Institute of Environmental Health and Safety postdoctoral training grant (M. W. L.: 5 T32 ESO7055).

Received 5/ 6/91. Accepted 12/13/91.