Abstract
Photodynamic therapy (PDT) is an approved modality for cancer treatment, which involves the administration of a photosensitive drug (PS) that is selectively accumulated in neoplastic tissues and their vasculature and subsequently can be activated with light at the appropriate wavelength to generate reactive molecular species that are toxic to tissues. In PDT, a great part of the used PS suffers degradation by light (photobleaching) that involves a decrease in the absorption and intensity of fluorescence of the photosensitizer as well as photoproduct formation evidenced by the appearance of a new absorption band. In this study, we investigated the correlation of cytotoxicity and depth of necrosis of Photogem and its photoproducts obtained previously by irradiation at 514 and 630 nm. The cytotoxicity for degraded Photogem decreases with the previous irradiation time of Photogem solution suggesting that the photoproducts of Photogem are less cytotoxics than the original formulation. A transition between the necrosed epithelium and healthy epithelium of normal liver of rats after irradiation at 630 nm was observed with irradiated and nonirradiated PS. It is observed that the depth of necrosis only at irradiation dose of 150 J/cm2 in both concentrations is greater for Photogem followed by Photogem degradated previously at 514 and then at 630 nm. The results obtained suggest that the threshold of necrosis values is lower for Photogem followed by its photoproducts formed, suggesting that the photoproducts present a low photodynamic activity. If the photosensitizer degradation happens at the same time as tumor destruction, the drug degradation can be complete before reaching the threshold of necrosis; then it is very important to control the drug concentration and light intensity of irradiation during PDT.
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References
S. Marchal et al., “Necrotic and Apoptotic Features of Cell Death in Response to Foscan Photosensitization of HT29 Monolayer and Multicell Spheroids,” Biochem. Pharmacol. 69(8), 1167 (2005).
A. Chwilkowska et al., “Uptake of Photofrin II, a Photosensitizer Used in Photodynamic Therapy, by Tumour Cells in Vitro,” Acta Biochim. Pol. 50, 509 (2003).
S. Sporri et al., “Effects of 5-Aminolaevulinic Acid on Human Ovarian Canser Cells and Human Vascular Endothelial Cells in vitro,” J. Photochem. Photobiol. B 64(1), 8 (2001).
N. Rousset et al., “Cellular Distribution and Phototoxicity of Benzoporphyrin Derivative and Photofrin,” Res. Exp. Med. (Berl) 199, 341 (2000).
C. H. Sibata, V. C. Colussi, N. O. Oleinick, and T. J. Kinsella, “Photodynamic Therapy in Oncology,” Expert Opin. Pharmacother 2, 917 (2001).
S. Banfi et al., “Photodynamic Effects of Porphyrin and Chlorin Photosensitizers in Human Colon Adenocarcinoma Cells,” Bioorg. Med. Chem. 12, 4853 (2004).
A. F. Mironov, A. N. Nizhnik, and A. Y. Nockel, “Hematoporphyrin Derivatives-an Oligomeric Composition Study,” J. Photochem. Photobiol., B 4, 297 (1990).
V. I. Chissov et al., “Photodynamic Therapy and Fluorescent Diagnosis of Malignant Tumors Using Preparation Photogem,” Khirurgiia (Mosk), No. 12, 3 (1994).
V. V. Sokolov et al., “Clinical Fluorescence Diagnostics in the Course of Photodynamic Therapy of Cancer with Photosensitizer Photogem®,” SPIE 2325, 375 (1995).
A. A. Stratonnikov, G. A. Meerovich, and V. B. Loschenov, “Photobleaching of Photosensitizers Applied for Photodynamic Therapy,” SPIE 3909, 81 (2000).
R. Rotomskis et al., “Phototransformation of Sensitisers: 3. Implications for Clinical Dosimetry,” Lasers Med. Sci. 13, 271 (1998).
R. Bonnett and G. Martinez, “Photobleaching of Sensitisers Used in Photodynamic Therapy,” Tetrahedron 57, 9513 (2001).
R. Rotomskis, G. Streckyte, and S. Bagdonas, “Phototransformations of Sensitizers: 1. Significance of the Nature of the Sensitizer in the Photobleaching Process and Photoproduct Formation in Aqueous Solution,” J. Photochem. Photobiol., B 39, 167 (1997).
C. Hadjur et al., “Spectroscopic Studies of Photobleaching and Photoproduct Formation of Meta (Tetrahydroxyphenyl) Chlorin (m-THPC) Used in Photodynamic Therapy. The Production of Singlet Oxygen by m-THPC,” Photochem. Photobiol. 45, 170 (1998).
M. S. Patterson, B. C. Wilson, and R. Graff, “In Vivo Tests of the Concept of Photodynamic Threshold Dose in Normal Rat Liver Photosensitized by Aluminum Chlorosulphonated Phthalocyanine,” Photochem. Photobiol. 51, 343 (1990).
L. I. Grossweiner, “PDT Light Dosimetry Revisited,” J. Photochem. Photobiol., B 38, 258 (1997).
W. R. Potter, T. S. Mang, and T. J. Dougherty, “The Theory of Photodynamic Therapy Dosimetry: Consequences of Photo-Destruction of Sensitizer,” Photochem. Photobiol. 46, 97 (1987).
J. Moan and D. Kessel, “Photoproduct Formed from Photofrin II in Cells,” J. Photochem. Photobiol., B 1, 429 (1988).
J. Moan, C. Rimington, and Z. Malik, “Photoinduced Degradation and Modification of Photofrin-II in Cells-in Vitro,” Photochem. Photobiol. 47, 363 (1988).
J. Moan and K. Berg, “The Photodegradation of Porphyrins in Cells Can Be Used to Estimate the Lifetime of Singlet Oxygen,” Photochem. Photobiol. 53, 549 (1991).
F. Denizot and R. Lang, “Rapid Colorimetric Assay for Cell Growth and Survival. Modifications to Die Tetrazolium Dye Procedure Giving Improved Sensitivity and Reliability,” J. Immunol. Methods 89, 271 (1986).
J. Carmichael et al., “Evaluation of a Tetrazoliuin-Based Semi-Automated Colorimetric Assay: Assessment of Chemosensitivity Testing,” Cancer Res. 47, 936 (1987).
T. H. M. Chou, CalcuSyn: Windows Software for Dose Effect Analysis (Biosoft, Cambridge, 1996).
T. J. Farrell et al., “Comparison of the in Vivo Photodynamic Threshold Dose for Photofrin, Mono-and Tetrasulfonated Aluminum Phthalocyanine Using a Rat Liver Model,” Photochem. Photobiol. 68, 394 (1998).
L. Lilge and B. C. Wilson, “Photodynamic Therapy of Intracranial Tissues: a Preclinical Comparative Study of Four Different Photosensitizers,” J. Clin. Laser Med. Surg. 16, 81 (1998).
J. Ferreira et al., “Necrosis Characteristics of Photodynamics Therapy in Normal Rat Liver,” Laser Phys. 14, 209 (2004).
J. Ferreira, “Experimental Determination of Threshold Dose in Photodynamic Therapy in Normal Rat Liver.” (in press, Laser. Phys. Lett.).
J. Ferreira et al., “Correlation between the Photostability and Photodynamic Efficacy for Different Photosensitizers,” Laser Phys. Lett. 3(2), 91 (2006).
S. G. Bown et al., “Photodynamic Therapy with Porphyrin and Phthalocyanine Sensitisation: Quantitative Studies in Normal Rat Liver,” Br. J. Cancer 54(1), 43 (1986).
N. R. Pimstone, I. J., Homer, J. Shaylor-Bellings, and S. N. Gandhi, “Haematoporphyrin Augmented Phototherapy: Dosimetry Studies in Experimental Liver Cancer in the Rat,” SPIE 357, 60 (1982).
P. F. C. Menezes et al., “Dark Cytotoxicity of the Photoproducts of the Photosensitizer Photogem after Photobleaching Induced by a Laser,” Laser Phys. 15, 435 (2005).
P. F. C. Menezes et al., “Cytotoxicity of the Photoproducts of the Photosensitizer Photogem Induced by Intense Illumination,” SPIE 5622, 51 (2004).
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Menezes, P.F.C., Imasato, H., Ferreira, J. et al. Correlation of cytotoxicity and depth of necrosis of the photoproducts of photogem®. Laser Phys. 17, 461–467 (2007). https://doi.org/10.1134/S1054660X0704024X
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DOI: https://doi.org/10.1134/S1054660X0704024X