Photodynamic treatment of cholangiocarcinoma with phthalocyanine compounds in laboratory animals (Conference Presentation)

The new generations of photoactive compounds, which are derivatives of already well-established groups of photosensitizers, together with the modern light sources in the spectral region of their activation and in the PDT window range, are emerging as a reliable phototherapy approach for tumour treatment with higher efficiency. The substitution of a highly hydrophobic phthalocyanine with galactose units could improve the solubility and to decrease significant aggregation in polar solvents. The control group of rats with transplanted cholangiocarcinoma without any treatment was used for comparison of PDT effectiveness. In the second group the white outbred male rats with cholangiocarcinoma lesions were treated using Zn-phthalocyanine, as a typical representative of phthalocyanine photosensitizers with known photodynamic properties and the third group of animals was treated with galactose – Lu-phthalocyanine, as a novel derivative from the same family with two specific differences – presence of galactose and replacing of Zn(II) with Lu(III) ion. To compare the PDT effectiveness of both compounds the same drug doses were applied - 2 mg/kg, applied by intratumoural injection. Diode laser source at 670 nm, on 50 mW output power with power density applied 200 mW/cm2 was applied for 1000 sec to obtain total irradiation dose of 200 J/cm2 for each lesion. 3 days after treatment, the animals were withdrawn from the experiment. Tissue from the central zone and periphery of the tumor was taken for morphological examination and fixed in 10% formalin. Serial paraffin sections were stained with hematoxilin-eosin and by immunohistochemical staining with antibodies to proliferation marker Ki-67 and apoptosis marker BAX. After photodynamic therapy, pronounced necrobiotic changes in combination with an inflammatory reaction were developed at the central zone of tumors. The dystrophic changes, reduction of proliferation and development of apoptosis in tumor cells were observed on tumor periphery as well.