29th Annual Meeting of the American Society of Photobiology

Downtown Marriot

Chicago, Il.

Photodynamic Activity of Phthalocyanine Photosensitizer Pc 4 on B16 Murine Melanoma.

Abstract-
Photodynamic therapy for the treatment of malignant melanoma is a highly desirable goal. Pc 4 has generally been unsuccessful because initial studies with HpD showed a poor response. Pc 4 is a silicon phthalocyanine photosensitizer, which has shown excellent PDT response in mouse skin tumors, implanted tumors and human tumor xenografts in athymic nude mice at doses that have little or no adverse effect, particularly cutanous photosensitization. In the present study, Pc 4 was evaluated in the B16 mouse, pigmented melanoma in vitro and in vivo. The LD₅₀ following Pc 4-PDT (15 kJ/cm², >600 nm) in B16 and radiation induced fibrosarcoma, RIF-1 cells were compared by the MTT assay and found to be 0.75 uM and 0.10 uM, respectively. Our earlier studies have shown that Pc 4-PDT is an efficient inducer of apoptosis in most cancer cells and tumors investigated. To quantify apoptosis following Pc 4-PDT in B16 cells, an ELISA assay was used to measure DNA fragmentation expressed as an enrichment factor. The greatest amount of DNA fragmentation was found at 0.75 uM Pc 4. For in vivo studies, B16 cells were implanted on the dorsum of C57 BL/6 mice. When the tumor size reached 40-60 mm³, Pc 4 was administered via tail vein at doses of 0.6 and 1.0 mg/kg b.w. Forty-eight hours post injection the animals were irradiated with a fluence of 150 mW/cm², 150 J/cm² at 672 nm. Tumor volume measurements were made daily following light exposure or until tumors reached four times the initial volume. For most of the treated tumors there was significant delay in regrowth, typically up to five days as compared to animals of all control groups. The present study suggests that Pc 4-PDT can suppress B16 malignant melanoma and merits evaluation for human melanoma.

Keywords: Pc 4-PDT, malignant melanoma, apoptosis