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Potential sensitizers for two-photon photodynamic therapy
198
Poster Abstracts
Results: A model predicting PS bleaching and depth of necrosis was obtained, with reasonable agreement to experimentation, although considering uniform distribution of PS and an estimative of oxygen concentration. A correlation parameter obtained by multiplying the normalized fluorescence by depth of necrosis values was determined to allow prediction of depth of necrosis by knowing the parameter for known irradiation conditions. Conclusion: This model could easily be used in clinical practice, as a simple approach to evaluate damage in tissues. doi:10.1016/j.pdpdt.2011.03.248 P042 Potential sensitizers for two-photon photodynamic therapy T. Timofeeva 1 , K. Odinets 2 1 2
Short 1 , D.
Sammeth 1 , T.
Kinnibrugh 1 , I.
New Mexico Highlands University, Las Vegas, NM 87701, USA Institute of Organoelement Compounds, Moscow 119991, Russia
Two-photon photodynamic therapy has the advantages of being highly localized in its effects and allows for deeper tissue penetration, when compared to one-photon photodynamic therapy. N-alkylated 3,5-bis(arylidene)-4-piperidones, with a donorpi-acceptor-pi-donor structure, have the potential to be useful two-photon sensitizers. We have measured two-photon cross sections (using femtosecond excitation), fluorescence quantum yields, fluorescence lifetimes, and X-ray crystal structures for a number of these compounds. Most two-photon cross sections are comparable to or larger than that of Rhodamine B. However, the fluorescence quantum yields are low (all less than 10%) and the fluorescence lifetimes are less than 1 ns (with one exception), suggesting that there may be a significant energy transfer to the triplet state. This would encourage singlet oxygen formation and increase cellular toxicity. Results of dark cyto-toxicity studies with several human cancer cell lines are presented. White light photo-toxicity results are also presented, and suggest that increasing the number of double bonds, from one to two, in the piperidone wings increases the photo-toxicity with little corresponding change in the dark cytotoxicity.
Figure 1 Theoretical fluence rate profile 5 mm from linear source plane. Methods: The parameters of an intensity decay model were experimentally determined for a 10 m long side-emitting fiber, and this equation was parameterized along the length of the rectangular, spiral pattern. This model generated a fluence rate profile that was verified with an initial prototype. Different inter-fiber spacings for the design were evaluated with the model to optimize fluence rate uniformity. Blanket performance on tissue phantom surface was also evaluated. Results: The optimal inter-fiber spacing for fluence rate spatial uniformity is 1 cm for a blanket area of 25 cm × 30 cm. The model predicts a significantly improved fluence rate (mean ± SD) of 44.8 ± 4.93 mW/cm2 in air for 1 W input power, 5 mm away from the fiber source plane (Fig. 1). Professional fabrication of this blanket design is underway and will include an intra-lipid solution layer to further improve the uniformity. Conclusion: The developed model provides a versatile, economic platform to compare and improve new blanket design patterns. The rectangular spiral design improves both uniformity and fiber utility for illumination. doi:10.1016/j.pdpdt.2011.03.250 P044 Analysis of the feasibility of the use of white LED and Photogem® in photodynamic therapy
doi:10.1016/j.pdpdt.2011.03.249 P043 A theoretical fluence rate profile model to design a spiral, spatially optimized fiber optic blanket for intra-operative photodynamic therapy P. Kundu, T. Zhu University of Pennsylvania, Department of Radiation Oncology, United States Introduction: Current photodynamic therapy treatment of malignant pleural or intra-peritoneal diseases uses a point source that compromises dose uniformity. While recent blanket prototypes using a single side-emitting fiber optic have improved uniformity, they are limited by intensity decay along fiber length. We develop a theoretical fluence rate distribution model to optimize the spacing of a new rectangular, spiral design for the fiber optic.
M.B. Requena 1 , L.T. Moriyama 2 , S. Pratavieira 2 , C. Kurachi 2 , V.S. Bagnato 2 1
Universidade Estadual Paulista, Brazil University of São Paulo, Instituto de Física de São Carlos, São Carlos, SP, Brazil 2
Most photodynamic therapy procedures use red light around 630 nm when haematoporphyrin derivative (HpD) is the sensitizer. This study aims to evaluate the feasibility of a white light source for PDT, through in vitro study of photosensitizer photodegradation and analysis of light propagation in turbid phantoms. The light source used was a white LED; Photogem® (Russia) was used as photosensitizer, and to simulate the in vitro response of biological tissue cellular membrane, a surfactant was added to the aqueous solution, which was illuminated for 60 minutes and the degradation was followed using fluorescence spectroscopy. For analysis of light penetration depth a turbid phantom based on fat emulsion was used. To collect light intensity data inside the turbid medium, we used an isotropic probe coupled to a spectrophotometer. A translation stage allowed probe displacement within the phantom and light intensity
Poster Abstracts
Results: A model predicting PS bleaching and depth of necrosis was obtained, with reasonable agreement to experimentation, although considering uniform distribution of PS and an estimative of oxygen concentration. A correlation parameter obtained by multiplying the normalized fluorescence by depth of necrosis values was determined to allow prediction of depth of necrosis by knowing the parameter for known irradiation conditions. Conclusion: This model could easily be used in clinical practice, as a simple approach to evaluate damage in tissues. doi:10.1016/j.pdpdt.2011.03.248 P042 Potential sensitizers for two-photon photodynamic therapy T. Timofeeva 1 , K. Odinets 2 1 2
Short 1 , D.
Sammeth 1 , T.
Kinnibrugh 1 , I.
New Mexico Highlands University, Las Vegas, NM 87701, USA Institute of Organoelement Compounds, Moscow 119991, Russia
Two-photon photodynamic therapy has the advantages of being highly localized in its effects and allows for deeper tissue penetration, when compared to one-photon photodynamic therapy. N-alkylated 3,5-bis(arylidene)-4-piperidones, with a donorpi-acceptor-pi-donor structure, have the potential to be useful two-photon sensitizers. We have measured two-photon cross sections (using femtosecond excitation), fluorescence quantum yields, fluorescence lifetimes, and X-ray crystal structures for a number of these compounds. Most two-photon cross sections are comparable to or larger than that of Rhodamine B. However, the fluorescence quantum yields are low (all less than 10%) and the fluorescence lifetimes are less than 1 ns (with one exception), suggesting that there may be a significant energy transfer to the triplet state. This would encourage singlet oxygen formation and increase cellular toxicity. Results of dark cyto-toxicity studies with several human cancer cell lines are presented. White light photo-toxicity results are also presented, and suggest that increasing the number of double bonds, from one to two, in the piperidone wings increases the photo-toxicity with little corresponding change in the dark cytotoxicity.
Figure 1 Theoretical fluence rate profile 5 mm from linear source plane. Methods: The parameters of an intensity decay model were experimentally determined for a 10 m long side-emitting fiber, and this equation was parameterized along the length of the rectangular, spiral pattern. This model generated a fluence rate profile that was verified with an initial prototype. Different inter-fiber spacings for the design were evaluated with the model to optimize fluence rate uniformity. Blanket performance on tissue phantom surface was also evaluated. Results: The optimal inter-fiber spacing for fluence rate spatial uniformity is 1 cm for a blanket area of 25 cm × 30 cm. The model predicts a significantly improved fluence rate (mean ± SD) of 44.8 ± 4.93 mW/cm2 in air for 1 W input power, 5 mm away from the fiber source plane (Fig. 1). Professional fabrication of this blanket design is underway and will include an intra-lipid solution layer to further improve the uniformity. Conclusion: The developed model provides a versatile, economic platform to compare and improve new blanket design patterns. The rectangular spiral design improves both uniformity and fiber utility for illumination. doi:10.1016/j.pdpdt.2011.03.250 P044 Analysis of the feasibility of the use of white LED and Photogem® in photodynamic therapy
doi:10.1016/j.pdpdt.2011.03.249 P043 A theoretical fluence rate profile model to design a spiral, spatially optimized fiber optic blanket for intra-operative photodynamic therapy P. Kundu, T. Zhu University of Pennsylvania, Department of Radiation Oncology, United States Introduction: Current photodynamic therapy treatment of malignant pleural or intra-peritoneal diseases uses a point source that compromises dose uniformity. While recent blanket prototypes using a single side-emitting fiber optic have improved uniformity, they are limited by intensity decay along fiber length. We develop a theoretical fluence rate distribution model to optimize the spacing of a new rectangular, spiral design for the fiber optic.
M.B. Requena 1 , L.T. Moriyama 2 , S. Pratavieira 2 , C. Kurachi 2 , V.S. Bagnato 2 1
Universidade Estadual Paulista, Brazil University of São Paulo, Instituto de Física de São Carlos, São Carlos, SP, Brazil 2
Most photodynamic therapy procedures use red light around 630 nm when haematoporphyrin derivative (HpD) is the sensitizer. This study aims to evaluate the feasibility of a white light source for PDT, through in vitro study of photosensitizer photodegradation and analysis of light propagation in turbid phantoms. The light source used was a white LED; Photogem® (Russia) was used as photosensitizer, and to simulate the in vitro response of biological tissue cellular membrane, a surfactant was added to the aqueous solution, which was illuminated for 60 minutes and the degradation was followed using fluorescence spectroscopy. For analysis of light penetration depth a turbid phantom based on fat emulsion was used. To collect light intensity data inside the turbid medium, we used an isotropic probe coupled to a spectrophotometer. A translation stage allowed probe displacement within the phantom and light intensity