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PDT
Photodiagnosis and Photodynamic Therapy (2011) 8, 123—125
available at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/pdpdt
Plenary Abstracts
PL02 Targeted PDT and its clinical relevance T. Hasan Harvard Med.School/Mass.General Hosp, Wellman Ctr for Photomed, Boston, MA,USA PDT is applied to a number of cancer and non-cancer pathologies fairly routinely yet remains primarily palliative. A perceived limitation of PDT is that it is a localized therapy and has little benefit in widespread disease. However, a little appreciated potential of PDT is that with appropriate targeting it could be used in fairly large loco-regional treatments and with thoughtful combinations with other treatments, it could impact systemic disease. In the case of cancer, it is becoming increasingly clear that no single treatment approach is adequate for cure or even long term control of the disease. Multiple molecular pathways that interact with each other operate to keep tumors viable and resistant to routine treatments. While being a problem, this molecular conversation opens up the possibilities of targeting these pathways and provides new molecular targets that can be exploited for treatment enhancement. In addition, several laboratories have reported an activation or deactivation of these critical pathways with photosensitization so as to sensitize target cells to neutralization by specific inhibitors in combination with PDT. For convenience, targeted PDT maybe classified into three broad categories. (1) Increased accumulation of the photosensitizers (PS) in target cells or tissues. This is accomplished by binding the PS to targeted delivery vehicles such as antibodies, polymers and others. Included within this broad category of delivery enhanced targeting is the whole field of nanotechnology that provides the option of delivering high payloads of PS and other adjunct agents to the right place at the right time. A second method for enhancing PS accumulation is by the biological modulation of target sites. An elegant example of this is in the case of ALA-PDT where molecular interventions altering the differentiation or enzyme status of cells led to enhanced PDT outcomes. (2) Mechanismbased combinations. Molecular targets are identified from careful mechanistic studies and appropriate combinations with PDT are strategized to obtain enhanced treatment outcomes. Examples of this approach include PDT combinations with anti VEGF agents. (3) Functional targeting. In this approach, PS design is based on a cellular function specific to target cells of interest so as to lend exquisite specificity of PS localization only in or around the target cells of interest that express the particular molecular characteristics being 1572-1000/$ — see front matter doi:10.1016/j.pdpdt.2011.03.196
exploited. The most frequent example of this category of targeting is the development of photosensitizers with enzyme cleavable linkages. There are numerous iterations of the above approaches and a few of them are either being used in the clinic or are entering clinical trials. This presentation will include an overview of targeted PDT along with a perspective of these approaches in clinical PDT. doi:10.1016/j.pdpdt.2011.03.197 PL03 ALA and its impact on PDD/PDT J. Kennedy Queen’s University, Department of Oncology, Kingston, Ontario, Canada This will be a very personal history of the development of PDD/PDT, as remembered by one who was a participant in that history from very early times. It will consist of a series of personal ‘‘snapshots’’ of selected events from the 1970’s up to the present. As with all such personal histories, it will not cover every important development in the field, but it should be interesting, and it might even be fun! At the very least it will provide some insight into the joy and excitement that biomedical research can provide. doi:10.1016/j.pdpdt.2011.03.198 PL04 FLIM and SLIM for autofluorescence and PDD: New algorithms A. Rueck ∗ , F. Dolp, J. Breymeyer, D. Strat ILM, Ulm, Germany Fluorescence guided tumor resection is very well accepted in the case of bladder cancer and brain tumor, respectively. However, false positive results are one of the major problems, which will make the discrimination between tumor tissue and inlammation difficult. In contrast fluorescence lifetime imaging (FLIM) and especially spectral resolved FLIM (SLIM) [1] can significantly improve the analysis. The fluorescence decay of a fluorophore in many cases does not show a simple monoexponential profile. A very complex situ-
available at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/pdpdt
Plenary Abstracts
PL02 Targeted PDT and its clinical relevance T. Hasan Harvard Med.School/Mass.General Hosp, Wellman Ctr for Photomed, Boston, MA,USA PDT is applied to a number of cancer and non-cancer pathologies fairly routinely yet remains primarily palliative. A perceived limitation of PDT is that it is a localized therapy and has little benefit in widespread disease. However, a little appreciated potential of PDT is that with appropriate targeting it could be used in fairly large loco-regional treatments and with thoughtful combinations with other treatments, it could impact systemic disease. In the case of cancer, it is becoming increasingly clear that no single treatment approach is adequate for cure or even long term control of the disease. Multiple molecular pathways that interact with each other operate to keep tumors viable and resistant to routine treatments. While being a problem, this molecular conversation opens up the possibilities of targeting these pathways and provides new molecular targets that can be exploited for treatment enhancement. In addition, several laboratories have reported an activation or deactivation of these critical pathways with photosensitization so as to sensitize target cells to neutralization by specific inhibitors in combination with PDT. For convenience, targeted PDT maybe classified into three broad categories. (1) Increased accumulation of the photosensitizers (PS) in target cells or tissues. This is accomplished by binding the PS to targeted delivery vehicles such as antibodies, polymers and others. Included within this broad category of delivery enhanced targeting is the whole field of nanotechnology that provides the option of delivering high payloads of PS and other adjunct agents to the right place at the right time. A second method for enhancing PS accumulation is by the biological modulation of target sites. An elegant example of this is in the case of ALA-PDT where molecular interventions altering the differentiation or enzyme status of cells led to enhanced PDT outcomes. (2) Mechanismbased combinations. Molecular targets are identified from careful mechanistic studies and appropriate combinations with PDT are strategized to obtain enhanced treatment outcomes. Examples of this approach include PDT combinations with anti VEGF agents. (3) Functional targeting. In this approach, PS design is based on a cellular function specific to target cells of interest so as to lend exquisite specificity of PS localization only in or around the target cells of interest that express the particular molecular characteristics being 1572-1000/$ — see front matter doi:10.1016/j.pdpdt.2011.03.196
exploited. The most frequent example of this category of targeting is the development of photosensitizers with enzyme cleavable linkages. There are numerous iterations of the above approaches and a few of them are either being used in the clinic or are entering clinical trials. This presentation will include an overview of targeted PDT along with a perspective of these approaches in clinical PDT. doi:10.1016/j.pdpdt.2011.03.197 PL03 ALA and its impact on PDD/PDT J. Kennedy Queen’s University, Department of Oncology, Kingston, Ontario, Canada This will be a very personal history of the development of PDD/PDT, as remembered by one who was a participant in that history from very early times. It will consist of a series of personal ‘‘snapshots’’ of selected events from the 1970’s up to the present. As with all such personal histories, it will not cover every important development in the field, but it should be interesting, and it might even be fun! At the very least it will provide some insight into the joy and excitement that biomedical research can provide. doi:10.1016/j.pdpdt.2011.03.198 PL04 FLIM and SLIM for autofluorescence and PDD: New algorithms A. Rueck ∗ , F. Dolp, J. Breymeyer, D. Strat ILM, Ulm, Germany Fluorescence guided tumor resection is very well accepted in the case of bladder cancer and brain tumor, respectively. However, false positive results are one of the major problems, which will make the discrimination between tumor tissue and inlammation difficult. In contrast fluorescence lifetime imaging (FLIM) and especially spectral resolved FLIM (SLIM) [1] can significantly improve the analysis. The fluorescence decay of a fluorophore in many cases does not show a simple monoexponential profile. A very complex situ-