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PD products
150 the device herself and disposes of it as electronic waste. In an on-going study, the first patients have been treated with the new PDT procedure to document feasibility of the procedure.
Oral Abstracts O083 Dosimetry: Difficulties of quantifying the ‘amounts’ of singlet oxygen and other ROS in single cell photosensitized experiments P.R. Ogilby Chemistry Department, Aarhus University, Aarhus, Denmark A key aspect of mechanistic studies of oxygen-dependent photosensitized cell death is to quantify the amount of the respective reactive oxygen species (ROS) formed upon exposure of a given sample to light. Despite the fact that the amount of light delivered to a sample can be accurately measured for a wide range of experimental conditions, quantifying the amount of light absorbed and the efficiencies with which ROS are subsequently produced is a non-trivial exercise for many biological samples. In this lecture, I will address some of the difficulties associated with quantifying the amounts of photosensitized ROS production in experiments performed at the single cell level using both one- and two-photon excitation.
Results: Preliminary results from the first patients using the new combination device showed an excellent safety profile with no clinically relevant side effects. The HAL ointment and device was easily administered to the cervix and patients could easily use it during normal daily activities. Removal after 10—24 h was acceptable to the patients. Conclusion: HAL PDT using a new intravaginal device introduces a commercially attractive treatment modality for patients with cervical HPV infection and precancer. Preliminary safety results are encouraging and new studies to investigate clinical efficacy are in progress in Europe and US. doi:10.1016/j.pdpdt.2011.03.090 O082 How to get regulatory approval of PDT/PD products A.G. Horten, I.M. Lindvig Photocure ASA, Oslo, Norway Introduction: Photodynamic therapy (PDT) is a regulatory challenge as it combines a drug and light source. Regulatory challenges for PDT products are being discussed in this presentation. Results: Regulatory guidelines are often generic, whereas development decisions are specific to disease, treatment modality and actual results. Keeping authorities informed about the project specific development strategy is an important component for getting PDT products approved, as is understanding of the regulatory expectations to be incorporated in development plans and communications with authorities. The approval requirements in EU and the US are relatively similar, but close contact with both FDA and the European agencies is recommended to ensure expectations are met. These two PDT components constitute a so-called drug device combination product. Regulatory approval of both components needs to be secured. The approvals of the device and the drug are granted by different entities at the regulator’s end. Furthermore, approval processes of the device component in EU and the US are different. Marketing of medical devices in EU is based on ‘‘third party’’ certifications and the declaration of conformity with the MD directive. In the US, light sources for use in PDT are normally subject to a so-called Pre Market Approval (PMA) involving submission and assessment of detailed documentation of the device for approval by FDA. Conclusion: Due to the nature of PDT products, it is important to ensure close regulatory contact to align both drug and device sections of the agencies in the approval process. doi:10.1016/j.pdpdt.2011.03.091
doi:10.1016/j.pdpdt.2011.03.092 O084 Singlet oxygen in photodynamic therapy and beyond: Production and detection S. Nonell Universitat Ramon Llull, Institut Quimic de Sarria, Barcelona, Spain Singlet oxygen, a dioxygen molecule in its lower electronic excited state O2 (a1 g ), is regarded as a key mediator of a large number of chemical and biological processes. This presentation will provide an overview of the physical and chemical properties of singlet oxygen in relation to other reactive oxygen species. Also, the potential sources of singlet oxygen in biological systems will be examined, ranging from dark chemical and enzymatic reactions to intended or unwanted photosensitisation under ultraviolet, visible or near-infrared radiation. The main factors affecting the latter processes will be discussed with the aid of relevant examples from the literature. Finally, the techniques available to detect singlet oxygen in biological systems will be reviewed. doi:10.1016/j.pdpdt.2011.03.093 O086 Localized photo-oxidative burst stimulates de-novo ROS/RNS generation and apoptosis in bystander cells that propagate radialy through intercellular gap junctions A. Scherz 1 , Y. Salomon 2 , I. Pinkas 1 , I. Fein 1 1 2
Department of Plant Sciences, Weizmann Institute, Israel Department of biological regulation, Weizmann Institute, Israel
Background: O2 − and • OH and not singlet oxygen mediate the photodynamic effect of WST09 and WST11 [1,2]. Vascular-targeted photodynamic therapy (VTP) with WST09/WST11 primarily targets the tumor blood vessels [3]. Hence, we explored the response of bEnd.3 and H5 V endothelial cells (EC) in cultures to an oxidative burst (OB) generated upon WST11-VTP of confined (300 × 300 m) group of cells following pre-incubation with WST11. Methods: Ca2+ , ROS and RNS generation, membrane integrity and EC apoptosis were monitored at sub-cellular resolution by time-lapse fluorescence microscopy during 24 h post illumination in cultures of WT and genetically manipulated cells. Results: The acute OB confined to a few ECs, sensitized Ca2+ elevation followed by de-novo generation of ROS and RNS in bystander cells. The bystander cells generated ROS and RNS in their neigh-
Oral Abstracts O083 Dosimetry: Difficulties of quantifying the ‘amounts’ of singlet oxygen and other ROS in single cell photosensitized experiments P.R. Ogilby Chemistry Department, Aarhus University, Aarhus, Denmark A key aspect of mechanistic studies of oxygen-dependent photosensitized cell death is to quantify the amount of the respective reactive oxygen species (ROS) formed upon exposure of a given sample to light. Despite the fact that the amount of light delivered to a sample can be accurately measured for a wide range of experimental conditions, quantifying the amount of light absorbed and the efficiencies with which ROS are subsequently produced is a non-trivial exercise for many biological samples. In this lecture, I will address some of the difficulties associated with quantifying the amounts of photosensitized ROS production in experiments performed at the single cell level using both one- and two-photon excitation.
Results: Preliminary results from the first patients using the new combination device showed an excellent safety profile with no clinically relevant side effects. The HAL ointment and device was easily administered to the cervix and patients could easily use it during normal daily activities. Removal after 10—24 h was acceptable to the patients. Conclusion: HAL PDT using a new intravaginal device introduces a commercially attractive treatment modality for patients with cervical HPV infection and precancer. Preliminary safety results are encouraging and new studies to investigate clinical efficacy are in progress in Europe and US. doi:10.1016/j.pdpdt.2011.03.090 O082 How to get regulatory approval of PDT/PD products A.G. Horten, I.M. Lindvig Photocure ASA, Oslo, Norway Introduction: Photodynamic therapy (PDT) is a regulatory challenge as it combines a drug and light source. Regulatory challenges for PDT products are being discussed in this presentation. Results: Regulatory guidelines are often generic, whereas development decisions are specific to disease, treatment modality and actual results. Keeping authorities informed about the project specific development strategy is an important component for getting PDT products approved, as is understanding of the regulatory expectations to be incorporated in development plans and communications with authorities. The approval requirements in EU and the US are relatively similar, but close contact with both FDA and the European agencies is recommended to ensure expectations are met. These two PDT components constitute a so-called drug device combination product. Regulatory approval of both components needs to be secured. The approvals of the device and the drug are granted by different entities at the regulator’s end. Furthermore, approval processes of the device component in EU and the US are different. Marketing of medical devices in EU is based on ‘‘third party’’ certifications and the declaration of conformity with the MD directive. In the US, light sources for use in PDT are normally subject to a so-called Pre Market Approval (PMA) involving submission and assessment of detailed documentation of the device for approval by FDA. Conclusion: Due to the nature of PDT products, it is important to ensure close regulatory contact to align both drug and device sections of the agencies in the approval process. doi:10.1016/j.pdpdt.2011.03.091
doi:10.1016/j.pdpdt.2011.03.092 O084 Singlet oxygen in photodynamic therapy and beyond: Production and detection S. Nonell Universitat Ramon Llull, Institut Quimic de Sarria, Barcelona, Spain Singlet oxygen, a dioxygen molecule in its lower electronic excited state O2 (a1 g ), is regarded as a key mediator of a large number of chemical and biological processes. This presentation will provide an overview of the physical and chemical properties of singlet oxygen in relation to other reactive oxygen species. Also, the potential sources of singlet oxygen in biological systems will be examined, ranging from dark chemical and enzymatic reactions to intended or unwanted photosensitisation under ultraviolet, visible or near-infrared radiation. The main factors affecting the latter processes will be discussed with the aid of relevant examples from the literature. Finally, the techniques available to detect singlet oxygen in biological systems will be reviewed. doi:10.1016/j.pdpdt.2011.03.093 O086 Localized photo-oxidative burst stimulates de-novo ROS/RNS generation and apoptosis in bystander cells that propagate radialy through intercellular gap junctions A. Scherz 1 , Y. Salomon 2 , I. Pinkas 1 , I. Fein 1 1 2
Department of Plant Sciences, Weizmann Institute, Israel Department of biological regulation, Weizmann Institute, Israel
Background: O2 − and • OH and not singlet oxygen mediate the photodynamic effect of WST09 and WST11 [1,2]. Vascular-targeted photodynamic therapy (VTP) with WST09/WST11 primarily targets the tumor blood vessels [3]. Hence, we explored the response of bEnd.3 and H5 V endothelial cells (EC) in cultures to an oxidative burst (OB) generated upon WST11-VTP of confined (300 × 300 m) group of cells following pre-incubation with WST11. Methods: Ca2+ , ROS and RNS generation, membrane integrity and EC apoptosis were monitored at sub-cellular resolution by time-lapse fluorescence microscopy during 24 h post illumination in cultures of WT and genetically manipulated cells. Results: The acute OB confined to a few ECs, sensitized Ca2+ elevation followed by de-novo generation of ROS and RNS in bystander cells. The bystander cells generated ROS and RNS in their neigh-