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Antimicrobial PDT: Strategies for optimization and prospective applications in clinic and environment
124 ation arises, when more than one compound has to be analyzed. This could be the case when endogenous fluorophores of living cells and tissues have to be discriminated to identify oxidative metabolic changes (reviewed in Ref. [2]). Other examples are PDT, when different photosensitizer metabolites are observed simultaneously. In those cases a considerable improvement could be achieved when time-resolved and spectral-resolved techniques are simultaneously incorporated. Within this presentation the principles of spectral and timeresolved fluorescence imaging and new algorithms [3] will be discussed together with a short overview on successful applications reported in the literature.
References [1] Rück A, Hülshoff CH, Kinzler I, Becker W, Steiner R. SLIM: A new method for molecular imaging. Micr Res Techn 2007;70:485—92. [2] Chorvat Jr D, Chorvatova A. Multi-wavelength fluorescence lifetime spectroscopy: A new approach to the study of endogenous fluorescence in living cells and tissues. Laser Phys Lett 2009;6(3):175—93. [3] D. Strat, F. Dolp, B. von Einem, C. Steinmetz, C.A.F. von Arnim, A. Rueck, Spectrally resolved fluorescence lifetime imaging microscopy (SLIM): FRET Global analysis with a one- and twoexponential donor model, JBO 16 (2), in press. doi:10.1016/j.pdpdt.2011.03.199 PL05 PDT in dermatology—A success story A. Sidoroff Medical University of Innsbruck, Department of Dermatology, Innsbruck, Austria From its very beginnings photodynamic therapy (PDT) was used to target dermatological diseases. With the introduction of topically applicable sensitizer (precursor)s a simple treatment modality became available. Not primarily company-driven, basic research and a large number of treated patients led to a good comprehension of the mechanisms and a realistic estimation of the clinical potential of this method: PDT was a promising new approach in the treatment of epithelial non-melanoma skin cancer (NMSC). The next step had to be randomized controlled trials (with topical aminolevulinic acid or its methyl ester) to make PDT a treatment approved by regulatory authorities. PDT is now a highly accepted procedure in dermatology based on a very good level of evidence for its efficacy and advantages. The last obstacle that has to be overcome is the reimbursement situation in different countries but already now PDT has provided help and cure for many thousands of patients suffering from dermatological problems. doi:10.1016/j.pdpdt.2011.03.200 PL06 Antimicrobial PDT: Strategies for optimization and prospective applications in clinic and environment G. Jori Department of Biology, University of Padova, Italy PDT of infectious diseases of microbial origin is based on the property of selected photosensitising agents, especially those characterized by the presence of positively charged functional groups, to readily bind with the outer wall of bacterial, fungal and protozoan cells; once activated by irradiation with visible light, the
Plenary Abstracts photosensitisers generate reactive oxygen species which induce the irreversible modification of specific constituents of the wall. The consequent enhanced permeability of the wall allows sufficiently large doses of the photosensitiser to penetrate to the cytoplasmic membrane. The photoprocess then involves a number of endocellular activities (e.g., enzymic catalysis, metabolic pathways) whose integrity is critical for cell survival. The genetic material is generally involved in the late stage of the photoprocess, which minimizes the probability of inducing mutagenic processes. Favourable features of PDT include: (a) the possibility to develop treatment regimes acting on most classes of microbial pathogens, including Gram-positive and Gram-negative bacteria, yeasts, fungi and parasitic protozoa, and even highly resistant microbial lifeforms such as bacterial spores and parasite cysts; (b) the high susceptibility to PDT exhibited by antibiotic-resistant microbial strains; (c) the selectivity of microbial cell killing in comparison with the constituents of host tissues; (d) the low risk of inducing mutagenic effects; (e) the possibility to activate the photodynamic sensitisers by means of inexpensive and safe visible light sources. PDT can be easily applied for the therapy of infections in external readily accessible organs, through topical application of the photosensitiser taking advantage of the availability of several skinpenetrating delivery systems. The continuous progresses in optical fibre technology make even deep-seated infections amenable to the photodynamic approach. Clinical applications of antimicrobial PDT are most widespread for treatment of periodontitis, acne and infected leg ulcers. Recent findings suggest that this technique can be also exploited for addressing a number of environmental problems of high scientific and social impact: a significant number of man-made activities cause the deterioration of the environment promoting the proliferation of potentially dangerous microbial strains which often find a favourable habitat in humid sites, and this can spread epidemic diseases over large distances. As a consequence, in addition to human patients, several constituents of the various ecosystems are at serious risk of being affected by infectious diseases. In this connection, antimicrobial PDT was found to play a major role for the prevention or cure of water-borne diseases and the control of harmful microorganisms and insects in aqueous media. doi:10.1016/j.pdpdt.2011.03.201 PL08 A systematic review of photodynamic therapy for high grade gliomas Isaac Phang 2,∗ , Sam Eljamel 1 1
The University of Dundee, Scotland, United Kingdom The Southren General Hospital Glasgow, Scotland, United Kingdom 2
High grade intracranial gliomas have a poor survival despite cytoreductive surgery and chemoradiotherapy. Cytoreduction has been correlated with better outcome, and photodynamic therapy, in conjunction with surgery, is postulated to afford better local disease control. We performed systematic literature review in April 2010 using the Medline, EMBASE and COCHRANE databases. ‘‘Glioma’’ and ‘‘photodynamic’’ were used as search terms. Only clinical articles in English with WHO grade III/IV (new or recurrent) gliomas with survival data were selected. The reference lists of the selected papers were also searched. 214 papers and 89 papers were identified in Medline and EMBASE respectively using the search terms. There were no studies identified in the COCHRANE database. Excluding laboratory articles, articles not in English and articles without survival data and cytoreductive surgery, 11 papers were identified. 1 paper was excluded because of duplication. Hand-searching of the identified references yielded 1 additional paper. Almost all PDT
References [1] Rück A, Hülshoff CH, Kinzler I, Becker W, Steiner R. SLIM: A new method for molecular imaging. Micr Res Techn 2007;70:485—92. [2] Chorvat Jr D, Chorvatova A. Multi-wavelength fluorescence lifetime spectroscopy: A new approach to the study of endogenous fluorescence in living cells and tissues. Laser Phys Lett 2009;6(3):175—93. [3] D. Strat, F. Dolp, B. von Einem, C. Steinmetz, C.A.F. von Arnim, A. Rueck, Spectrally resolved fluorescence lifetime imaging microscopy (SLIM): FRET Global analysis with a one- and twoexponential donor model, JBO 16 (2), in press. doi:10.1016/j.pdpdt.2011.03.199 PL05 PDT in dermatology—A success story A. Sidoroff Medical University of Innsbruck, Department of Dermatology, Innsbruck, Austria From its very beginnings photodynamic therapy (PDT) was used to target dermatological diseases. With the introduction of topically applicable sensitizer (precursor)s a simple treatment modality became available. Not primarily company-driven, basic research and a large number of treated patients led to a good comprehension of the mechanisms and a realistic estimation of the clinical potential of this method: PDT was a promising new approach in the treatment of epithelial non-melanoma skin cancer (NMSC). The next step had to be randomized controlled trials (with topical aminolevulinic acid or its methyl ester) to make PDT a treatment approved by regulatory authorities. PDT is now a highly accepted procedure in dermatology based on a very good level of evidence for its efficacy and advantages. The last obstacle that has to be overcome is the reimbursement situation in different countries but already now PDT has provided help and cure for many thousands of patients suffering from dermatological problems. doi:10.1016/j.pdpdt.2011.03.200 PL06 Antimicrobial PDT: Strategies for optimization and prospective applications in clinic and environment G. Jori Department of Biology, University of Padova, Italy PDT of infectious diseases of microbial origin is based on the property of selected photosensitising agents, especially those characterized by the presence of positively charged functional groups, to readily bind with the outer wall of bacterial, fungal and protozoan cells; once activated by irradiation with visible light, the
Plenary Abstracts photosensitisers generate reactive oxygen species which induce the irreversible modification of specific constituents of the wall. The consequent enhanced permeability of the wall allows sufficiently large doses of the photosensitiser to penetrate to the cytoplasmic membrane. The photoprocess then involves a number of endocellular activities (e.g., enzymic catalysis, metabolic pathways) whose integrity is critical for cell survival. The genetic material is generally involved in the late stage of the photoprocess, which minimizes the probability of inducing mutagenic processes. Favourable features of PDT include: (a) the possibility to develop treatment regimes acting on most classes of microbial pathogens, including Gram-positive and Gram-negative bacteria, yeasts, fungi and parasitic protozoa, and even highly resistant microbial lifeforms such as bacterial spores and parasite cysts; (b) the high susceptibility to PDT exhibited by antibiotic-resistant microbial strains; (c) the selectivity of microbial cell killing in comparison with the constituents of host tissues; (d) the low risk of inducing mutagenic effects; (e) the possibility to activate the photodynamic sensitisers by means of inexpensive and safe visible light sources. PDT can be easily applied for the therapy of infections in external readily accessible organs, through topical application of the photosensitiser taking advantage of the availability of several skinpenetrating delivery systems. The continuous progresses in optical fibre technology make even deep-seated infections amenable to the photodynamic approach. Clinical applications of antimicrobial PDT are most widespread for treatment of periodontitis, acne and infected leg ulcers. Recent findings suggest that this technique can be also exploited for addressing a number of environmental problems of high scientific and social impact: a significant number of man-made activities cause the deterioration of the environment promoting the proliferation of potentially dangerous microbial strains which often find a favourable habitat in humid sites, and this can spread epidemic diseases over large distances. As a consequence, in addition to human patients, several constituents of the various ecosystems are at serious risk of being affected by infectious diseases. In this connection, antimicrobial PDT was found to play a major role for the prevention or cure of water-borne diseases and the control of harmful microorganisms and insects in aqueous media. doi:10.1016/j.pdpdt.2011.03.201 PL08 A systematic review of photodynamic therapy for high grade gliomas Isaac Phang 2,∗ , Sam Eljamel 1 1
The University of Dundee, Scotland, United Kingdom The Southren General Hospital Glasgow, Scotland, United Kingdom 2
High grade intracranial gliomas have a poor survival despite cytoreductive surgery and chemoradiotherapy. Cytoreduction has been correlated with better outcome, and photodynamic therapy, in conjunction with surgery, is postulated to afford better local disease control. We performed systematic literature review in April 2010 using the Medline, EMBASE and COCHRANE databases. ‘‘Glioma’’ and ‘‘photodynamic’’ were used as search terms. Only clinical articles in English with WHO grade III/IV (new or recurrent) gliomas with survival data were selected. The reference lists of the selected papers were also searched. 214 papers and 89 papers were identified in Medline and EMBASE respectively using the search terms. There were no studies identified in the COCHRANE database. Excluding laboratory articles, articles not in English and articles without survival data and cytoreductive surgery, 11 papers were identified. 1 paper was excluded because of duplication. Hand-searching of the identified references yielded 1 additional paper. Almost all PDT