Uptake and photodynamic activity of porphycenes in tumor cells implanted on the chick chorioallantoic membrane (CAM)

Ronit Davidi; Varda Gottfried; Sol Kimel

doi:10.1117/12.230977

31 January 1996 Uptake and photodynamic activity of porphycenes in tumor cells implanted on the chick chorioallantoic membrane (CAM)

Ronit Davidi, Varda Gottfried, Sol Kimel

Author Affiliations +

Proceedings Volume 2625, Photochemotherapy: Photodynamic Therapy and Other Modalities; (1996) https://doi.org/10.1117/12.230977
Event: BiOS Europe '95, 1995, Barcelona, Spain

Abstract

The chick chorioallantoic membrane (CAM) is a convenient model for the study of photodynamic therapy (PDT). This membrane has a rich vasculature, which mimics the tumor neovasculature, and can also serve as a host for implanted tumors. The transparency of the CAM enables in-vivo monitoring of vascular changes during and post PDT, without the need to sacrifice test animals at each time point. Video documentation and analysis of events occurring during and after irradiation permit the quantification of changes in vessel morphology, blood perfusion and tumor development. The compounds tested in this study belong to a family of potential sensitizers -- the porphycenes. These are phorphyrin isomers based on a 16-membered macrocycle, in which the four methine moieties linking the pyrrole rings have been replaced by two direct bonds and two ethine bridges. Experiments were performed on blood vessels of the intact CAM and on recurrent human melanoma cells implanted on the CAM. Tumor selectivity was demonstrated by measuring drug uptake using fluorescence methods. A sensitizer injected systemically into the embryo yolk sac could be detected in the blood vessels 30 min after injection; 1 h later the sensitizer had preferentially accumulated in the tumor. Tumors were irradiated at the optimal uptake time (after 1 h) for 16 min with a 20 mW HeNe laser. Video image analysis showed that 96 h after irradiation tumors had decreased to 5% of their original size. In contrast, non-irradiated control tumors on the same CAM, continued to proliferate and grew to more than twice their original size. In addition, we observed a difference in the damage mechanism after systemic compared to topical administration. Topical application followed by irradiation caused fast necrosis of tumors, which might suggest direct damage to tumor cells, whereas after systemic administration, PDT damage was manifested by slower necrosis, presumably caused by vascular destruction.

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Ronit Davidi, Varda Gottfried, and Sol Kimel "Uptake and photodynamic activity of porphycenes in tumor cells implanted on the chick chorioallantoic membrane (CAM)", Proc. SPIE 2625, Photochemotherapy: Photodynamic Therapy and Other Modalities, (31 January 1996); https://doi.org/10.1117/12.230977

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