ABSTRACT
The efficacy of a new photosensitizer of chlorin E6 conjugated with a prostate-specific membrane antigen (PSMA) in photodynamic therapy of murine melanoma B16 was studied in in vivo experiments. The dynamics of photosensitizer accumulation in the tumor and surrounding tissues was evaluated and antitumor efficacy of photodynamic therapy was assessed by parameters of regression and morphological characteristics of experimental transplanted melanoma B16. The inhibitory effect of photodynamic therapy on melanoma was evaluated by complete regression of the tumor, absolute tumor growth coefficient in animals with continuation of tumor growth, and the increase in life span in comparison with the control; the criterion of cure was the absence of signs of tumor recurrence in mice within 90 days after therapy. The therapeutic potential of photodynamic therapy was determined by devitalization of tumor cells (histological examination of the zones of laser exposure on day 21 after treatment). The photosensitizer with PSMA-ligand exhibited high antitumor activity in photodynamic therapy for melanoma B16. Photodynamic therapy carried out at the optimum time after photosensitizer injection with experimentally determined parameters of laser exposure allows achieving the maximum inhibitory effect on melanoma. Pathomorphological study in the zones of exposure detected no survived tumor cells.
Subject(s)
Chlorophyllides/therapeutic use , Melanoma, Experimental/drug therapy , Photochemotherapy/methods , Skin Neoplasms/drug therapy , Urea/analogs & derivatives , Animals , Cell Line, Tumor , Chlorophyllides/chemistry , Chlorophyllides/pharmacokinetics , Female , Ligands , Melanoma, Experimental/diagnostic imaging , Melanoma, Experimental/metabolism , Melanoma, Experimental/pathology , Mice , Mice, Inbred C57BL , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacokinetics , Photosensitizing Agents/therapeutic use , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/metabolism , Skin Neoplasms/pathology , Urea/chemistry , Urea/pharmacokinetics , Urea/therapeutic useABSTRACT
We studied the effectiveness of photodynamic therapy with the photosensitizer Photoran E6 on the model of rat sarcoma M-1 positive for mutant p53 gene. Experiments showed that Photoran E6 exhibits high antitumor activity in photodynamic therapy of solid tumor of the connective tissue. Photodynamic therapy carried out during the optimal period after injections of Photoran E6 with the determined parameters of laser exposure allows achieving the maximum inhibitory effect on sarcoma M-1: 100% cured animals. Immunohistochemical study revealed no live tumor cells with expression of the mutant p53 protein in areas of photodynamic exposure.