Anne-Laure Bulin, F. Chaput, M. Broekgaarden, L. Sancey, J. Ravanat, T. Hasan, H. Elleaume
{"title":"Radioluminescent nanomaterials to induce deep-tissue PDT: towards a complete description of the therapeutic contributions (Conference Presentation)","authors":"Anne-Laure Bulin, F. Chaput, M. Broekgaarden, L. Sancey, J. Ravanat, T. Hasan, H. Elleaume","doi":"10.1117/12.2525832","DOIUrl":"https://doi.org/10.1117/12.2525832","url":null,"abstract":"","PeriodicalId":6365,"journal":{"name":"17th International Photodynamic Association World Congress","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79258405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Buzzá, M. D. Stringasci, C. Castro, R. H. S. Crestana, V. Bagnato, N. Inada
{"title":"Preliminaries results of clinical study of condylomas acuminate using PDT with new illumination devices (Conference Presentation)","authors":"H. Buzzá, M. D. Stringasci, C. Castro, R. H. S. Crestana, V. Bagnato, N. Inada","doi":"10.1117/12.2526160","DOIUrl":"https://doi.org/10.1117/12.2526160","url":null,"abstract":"","PeriodicalId":6365,"journal":{"name":"17th International Photodynamic Association World Congress","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90412264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Lilge, M. A. Munegowda, Carl J. Fisher, A. Mandel
Glioblastoma is a highly aggressive and common brain cancer in adults with a grave prognosis, and aggressive radio and chemotherapy provide only a 15 months median survival. We evaluated the tolerability, and efficacy of the Ruthenium-based photosensitizer TLD-1433 in the formulation with apo-Transferrin (Rutheriin®) in the RG2, rat glioblastoma model. The specific tumour uptake ratio, PDT threshold, of the RG2 rat glioblastoma models and normal brain in vivo were determined as well as the survival post-PDT and the extent of CD8+T cell infiltration post-PDT. Results were compared with those obtained by 5-ALA-induced PpIX mediated PDT in the same animal model. As both photosensitizers have different photophysical properties, the number of absorbed photons required to achieve an equal cell kill is compared during in-vitro and in vivo studies. A significantly lower absorbed energy was enough to achieve LD50 with Rutherrin® versus -PpIX mediated PDT. Rutherrin® provides higher selective uptake ratio (SUR>20) in RG2 tumours compared to normal brain, whereas the SUR for ALA-induced PpIX was 10.6 in the same tumour model. To evaluate the short-term tissue response in vivo enhanced T2-weighted MR images provided the spatial extent of edema, which is twice post PpIX-PDT versus Rutherrin®-PDT suggesting reduced non-specific damage typically associated with a secondary wave of neuronal damage. A significant survival increase was observed in Rutherrin® treated rats bearing RG2 versus PpIX-PDT for the selected treatment conditions, associated with an increased CD8+T cell infiltration in the tumours. Rutherrin®-PDT was well tolerated providing safe and effective treatment of RG2 -induced glioblastoma.
{"title":"Efficacy of ruthenium coordination complex based Rutherrin in a pre-clinical rat glioblastoma (GBM) model (Conference Presentation)","authors":"L. Lilge, M. A. Munegowda, Carl J. Fisher, A. Mandel","doi":"10.1117/12.2525608","DOIUrl":"https://doi.org/10.1117/12.2525608","url":null,"abstract":"Glioblastoma is a highly aggressive and common brain cancer in adults with a grave prognosis, and aggressive radio and chemotherapy provide only a 15 months median survival. We evaluated the tolerability, and efficacy of the Ruthenium-based photosensitizer TLD-1433 in the formulation with apo-Transferrin (Rutheriin®) in the RG2, rat glioblastoma model. The specific tumour uptake ratio, PDT threshold, of the RG2 rat glioblastoma models and normal brain in vivo were determined as well as the survival post-PDT and the extent of CD8+T cell infiltration post-PDT. Results were compared with those obtained by 5-ALA-induced PpIX mediated PDT in the same animal model. As both photosensitizers have different photophysical properties, the number of absorbed photons required to achieve an equal cell kill is compared during in-vitro and in vivo studies. A significantly lower absorbed energy was enough to achieve LD50 with Rutherrin® versus -PpIX mediated PDT. Rutherrin® provides higher selective uptake ratio (SUR>20) in RG2 tumours compared to normal brain, whereas the SUR for ALA-induced PpIX was 10.6 in the same tumour model. To evaluate the short-term tissue response in vivo enhanced T2-weighted MR images provided the spatial extent of edema, which is twice post PpIX-PDT versus Rutherrin®-PDT suggesting reduced non-specific damage typically associated with a secondary wave of neuronal damage. A significant survival increase was observed in Rutherrin® treated rats bearing RG2 versus PpIX-PDT for the selected treatment conditions, associated with an increased CD8+T cell infiltration in the tumours. Rutherrin®-PDT was well tolerated providing safe and effective treatment of RG2 -induced glioblastoma.","PeriodicalId":6365,"journal":{"name":"17th International Photodynamic Association World Congress","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86012757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lindsey Carlsen, T. Mandeville, Patrick C. Barrett, Evan Bradner, Tariq Sainuddin, S. McFarland, Sarah Chamberlain, D. Bellnier, G. Shafirstein
Ruthenium and osmium-based photosensitizers (PS) are compounds of interest for use in photodynamic therapy (PDT). These PS’s can be activated by light wavelengths in the range of 400-675 nm, which can be selected based on the tumor environment, treatment area, and available light sources. The objective of this study was to explore these PS’s for the treatment of several relatively aggressive cancer cell lines. A human adenocarcinoma cell line (A549) was treated with ruthenium-based compounds at concentrations of 1, 5, or 10 uM, followed by light treatment of 93 J/cm2 at either 532 nm or 630 nm. Similarly, osmium-based compounds were used to treat A549, murine melanoma (B16F10) and squamous cell carcinoma (SCCVII) cell lines at concentrations of 0.05, 1, or 3 uM, followed by light treatment of 93 J/cm2 at 630 nm. Cells survival was assessed 24 hours after PDT treatment using either alamarBlue or MTT cell viability assays. In-vitro MTT viability assays revealed that ruthenium-based compounds activated with 630 nm light showed high SCCVII cell toxicity at 5uM. AlamarBlue assays have shown that ruthenium based compounds activated by 532 nm light show high A549 cell toxicity at 1uM in-vitro. Osmium-based compounds showed optimal PDT-mediated cytotoxicity in SCCVII, A549, and B16F10 cell lines at a concentration of 1uM activated by 630 nm light, while exhibiting minimal dark toxicity. The Ruthenium and Osmium-based compounds are potentially potent PSs against lung, melanoma and squamous cell carcinoma cells, in-vitro.
{"title":"Novel metal-based photosensitizers for photodynamic therapy: exploratory study (Conference Presentation)","authors":"Lindsey Carlsen, T. Mandeville, Patrick C. Barrett, Evan Bradner, Tariq Sainuddin, S. McFarland, Sarah Chamberlain, D. Bellnier, G. Shafirstein","doi":"10.1117/12.2526180","DOIUrl":"https://doi.org/10.1117/12.2526180","url":null,"abstract":"Ruthenium and osmium-based photosensitizers (PS) are compounds of interest for use in photodynamic therapy (PDT). These PS’s can be activated by light wavelengths in the range of 400-675 nm, which can be selected based on the tumor environment, treatment area, and available light sources. The objective of this study was to explore these PS’s for the treatment of several relatively aggressive cancer cell lines. A human adenocarcinoma cell line (A549) was treated with ruthenium-based compounds at concentrations of 1, 5, or 10 uM, followed by light treatment of 93 J/cm2 at either 532 nm or 630 nm. Similarly, osmium-based compounds were used to treat A549, murine melanoma (B16F10) and squamous cell carcinoma (SCCVII) cell lines at concentrations of 0.05, 1, or 3 uM, followed by light treatment of 93 J/cm2 at 630 nm. Cells survival was assessed 24 hours after PDT treatment using either alamarBlue or MTT cell viability assays. In-vitro MTT viability assays revealed that ruthenium-based compounds activated with 630 nm light showed high SCCVII cell toxicity at 5uM. AlamarBlue assays have shown that ruthenium based compounds activated by 532 nm light show high A549 cell toxicity at 1uM in-vitro. Osmium-based compounds showed optimal PDT-mediated cytotoxicity in SCCVII, A549, and B16F10 cell lines at a concentration of 1uM activated by 630 nm light, while exhibiting minimal dark toxicity. The Ruthenium and Osmium-based compounds are potentially potent PSs against lung, melanoma and squamous cell carcinoma cells, in-vitro.","PeriodicalId":6365,"journal":{"name":"17th International Photodynamic Association World Congress","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86724851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Optical imaging guided photodynamic therapy monitoring and optimization (Conference Presentation)","authors":"U. Sunar","doi":"10.1117/12.2527344","DOIUrl":"https://doi.org/10.1117/12.2527344","url":null,"abstract":"","PeriodicalId":6365,"journal":{"name":"17th International Photodynamic Association World Congress","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83612018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
THIS IS FOR THE SESSION "CAPABILITIES OF 5-ALA" The accumulation of the fluorescent photosensitizer protoporphyrin IX (PpIX) after systemic administration of 5-ALA proved high tumor selectivity and led to intra-operative fluorescence guidance during resection of malignant glioma. 5-ALA therefore also promises to be useful for PDT of malignant glioma. Preclinical investigations resulted in the establishment of an appropriate treatment planning strategy and treatment parameters. This can be outlined as follows: interstitial placement of cylindrical diffuser fibers (1 to 4 cm diffuser length) by stereotaxy after careful planning on CT/MRI scans, such that fibers are approximately 1 cm apart and as close as 3-4 mm from the contrast uptaking tumor border. Aim of the irradiation parameters (200 mW/cm diffuser length for 1 hour) is to reach >95% photobleaching of PpIX in at least one optical penetration depth (approx. 3 mm) from the fibers. The therapeutic penetration depth can be expected to reach significantly deeper and kill glioma cells within parts of the infiltration zone, which are no more highlighted by Gd-contrast uptake. So far, inoperable de novo and recurrent malignant glioma with sizes up to 3 cm in diameter proved amenable in clinical investigations. Intriguing longterm progression free and overall survivals led to the design of prospective clinical trials, which are expected to start recruitment in 2019. Further research should focus on individualizing treatment parameters, further improve PpIX accumulation, including the sensitization of cancer stem cells and explore the role of immune stimulation by PDT, including the possible synergistic effect of immune checkpoint inhibitors.
{"title":"Interstitial photodynamic therapy (iPDT) of brain tumours (Conference Presentation)","authors":"H. Stepp, A. Rühm, R. Sroka, W. Stummer","doi":"10.1117/12.2526128","DOIUrl":"https://doi.org/10.1117/12.2526128","url":null,"abstract":"THIS IS FOR THE SESSION \"CAPABILITIES OF 5-ALA\"\u0000\u0000The accumulation of the fluorescent photosensitizer protoporphyrin IX (PpIX) after systemic administration of 5-ALA proved high tumor selectivity and led to intra-operative fluorescence guidance during resection of malignant glioma. 5-ALA therefore also promises to be useful for PDT of malignant glioma. Preclinical investigations resulted in the establishment of an appropriate treatment planning strategy and treatment parameters. This can be outlined as follows: interstitial placement of cylindrical diffuser fibers (1 to 4 cm diffuser length) by stereotaxy after careful planning on CT/MRI scans, such that fibers are approximately 1 cm apart and as close as 3-4 mm from the contrast uptaking tumor border. Aim of the irradiation parameters (200 mW/cm diffuser length for 1 hour) is to reach >95% photobleaching of PpIX in at least one optical penetration depth (approx. 3 mm) from the fibers. The therapeutic penetration depth can be expected to reach significantly deeper and kill glioma cells within parts of the infiltration zone, which are no more highlighted by Gd-contrast uptake. So far, inoperable de novo and recurrent malignant glioma with sizes up to 3 cm in diameter proved amenable in clinical investigations. Intriguing longterm progression free and overall survivals led to the design of prospective clinical trials, which are expected to start recruitment in 2019. \u0000\u0000Further research should focus on individualizing treatment parameters, further improve PpIX accumulation, including the sensitization of cancer stem cells and explore the role of immune stimulation by PDT, including the possible synergistic effect of immune checkpoint inhibitors.","PeriodicalId":6365,"journal":{"name":"17th International Photodynamic Association World Congress","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75941895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction. Multiple myeloma (MM) is a cancer of terminally differentiated plasma B-cells that originates in the hematopoietic bone marrow and accounts for 15-20% of all hematologic malignancies. Combination therapies are commonly prescribed to patients with relapsed/refractory MM, which necessitates the stratification of responding patients to minimize toxicities and improve quality of life. Very late antigen-4 (VLA-4) and cluster of differentiation 38 (CD38) are over-expressed proteins on MM cells. Here, we will demonstrate VLA-4 and CD38 targeted molecular imaging as potential surrogates for targeted therapy. Materials and Methods: Daratumumab (Janssen Biotech), CD38 targeted antibody, was provided by the Siteman Cancer Center pharmacy. Sulfo-Cyanine5 (Cy5) NHS ester (Lumiprobe) was conjugated resulting in a 5:1 dye to antibody ratio. In vivo fluorescence imaging was performed on fox chase severe combined immunodeficient beige mice bearing MM1.S-GFP subcutaneous myeloma tumors (n = 7). VLA-4 imaging was performed using a highly selective peptidomimetic ligand (LLP2A) for the activated form of VLA-4 in 5TGM1-GFP syngeneic mouse model. Results and Conclusion. Here we used selective near-infrared fluorescent probes LLP2A-Cy5 and daratumumab-Cy5 to target α4β1 and CD38 expression respectively in vitro and in vivo in relevant myeloma models. Specificity for α4β1 over expressing cells was maintained in vivo in medullar MM with 7-fold and 2-fold increase in LLP2A-Cy5 uptake into tumor-bearing bone marrow and spleen, respectively. Tumor uptake of the fluorescently-labelled daratumumab increased through the imaging period with tumor to blood ratio 7 days post-contrast nearly doubling relative to pre-contrast. We are validating molecular imaging approaches for targeted therapy.
{"title":"Molecularly targeted imaging in multiple myeloma (Conference Presentation)","authors":"M. Shokeen","doi":"10.1117/12.2529655","DOIUrl":"https://doi.org/10.1117/12.2529655","url":null,"abstract":"Introduction. Multiple myeloma (MM) is a cancer of terminally differentiated plasma B-cells that originates in the hematopoietic bone marrow and accounts for 15-20% of all hematologic malignancies. Combination therapies are commonly prescribed to patients with relapsed/refractory MM, which necessitates the stratification of responding patients to minimize toxicities and improve quality of life. Very late antigen-4 (VLA-4) and cluster of differentiation 38 (CD38) are over-expressed proteins on MM cells. Here, we will demonstrate VLA-4 and CD38 targeted molecular imaging as potential surrogates for targeted therapy. \u0000Materials and Methods: Daratumumab (Janssen Biotech), CD38 targeted antibody, was provided by the Siteman Cancer Center pharmacy. Sulfo-Cyanine5 (Cy5) NHS ester (Lumiprobe) was conjugated resulting in a 5:1 dye to antibody ratio. In vivo fluorescence imaging was performed on fox chase severe combined immunodeficient beige mice bearing MM1.S-GFP subcutaneous myeloma tumors (n = 7). VLA-4 imaging was performed using a highly selective peptidomimetic ligand (LLP2A) for the activated form of VLA-4 in 5TGM1-GFP syngeneic mouse model.\u0000\u0000Results and Conclusion. Here we used selective near-infrared fluorescent probes LLP2A-Cy5 and daratumumab-Cy5 to target α4β1 and CD38 expression respectively in vitro and in vivo in relevant myeloma models. Specificity for α4β1 over expressing cells was maintained in vivo in medullar MM with 7-fold and 2-fold increase in LLP2A-Cy5 uptake into tumor-bearing bone marrow and spleen, respectively. Tumor uptake of the fluorescently-labelled daratumumab increased through the imaging period with tumor to blood ratio 7 days post-contrast nearly doubling relative to pre-contrast. We are validating molecular imaging approaches for targeted therapy.","PeriodicalId":6365,"journal":{"name":"17th International Photodynamic Association World Congress","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90096190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Efficacy of photodynamic therapy with a new photosensitizer (talaporfin sodium) as a salvage treatment for local failure of esophageal cancer (Conference Presentation)","authors":"Mamoru Tanaka, H. Nishie, H. Kataoka","doi":"10.1117/12.2524521","DOIUrl":"https://doi.org/10.1117/12.2524521","url":null,"abstract":"","PeriodicalId":6365,"journal":{"name":"17th International Photodynamic Association World Congress","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81926518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"WST11-VTP (Tookad soluble)is safe in the luminal treatment of obstructing esophago-gastric cancer (Conference Presentation)","authors":"H. Gerdes","doi":"10.1117/12.2531893","DOIUrl":"https://doi.org/10.1117/12.2531893","url":null,"abstract":"","PeriodicalId":6365,"journal":{"name":"17th International Photodynamic Association World Congress","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74641919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. S. Bruijn, Wei Peng, T. Hagen, G. M. Dam, J. Roodenburg, M. Witjes, D. Robinson
Photodynamic therapy (PDT) has been used clinically for the treatment of head and neck cancer. The effectiveness of PDT is often strongly dependent on fluence rate. Targeted photo-immunotherapy (PIT) may reduce the adverse effects of non-targeted PDT. The in-vivo distribution of the anti-EGFR targeted conjugate Cetuximab-IRDye700DX was investigated. Vascular and tumor responses were determined with respect to fluence rate. Intra-vital confocal microscopy of skin-fold chambers with the EGFR-overexpressing OSC-19 tumor showed peak tumor fluorescence 24 hrs after administration. Tumor to normal ratio was 3.1±1.6 (n=8). Tumor vascular responses were determined by imaging rhodamine-dextran extravasation. Two hrs after illumination (24 hr DLI, 100 J.cm-2 at 50 mW.cm-2) showed no leakage in 3 of 4 animals and stasis in 1. Normal vasculature showed mild to severe constriction of larger vessels up to 48 hrs after illumination. Subcutaneous OSC-19 tumors were transdermally illuminated with 100 J.cm-2 at 20, 50 and 150 mW.cm-2. Control tumors took 5.3±1.1 days to grow to 200%. All animals treated with 20 mW.cm-2 showed no tumor up to 90 days post treatment (n=4) compared to 1 of 4 in the 50 and 150 mW.cm-2 groups. The remaining tumors reached 200% after 17.9±5.2 and 19.5±7.4 days. Crust formation of the overlying skin was observed at low fluence rate. Cetuximab-IRDye700DX showed significant tumor to normal ratio. Normal tissue responses like vascular effects and crust formation of the skin was observed and may be caused by conjugate still present in the circulation. The effect of targeted-PIT is strongly dependent on fluence rate.
{"title":"Epidermal growth factor receptor: targeted photoimmunotherapy is fluence rate dependent in-vivo (Conference Presentation)","authors":"H. S. Bruijn, Wei Peng, T. Hagen, G. M. Dam, J. Roodenburg, M. Witjes, D. Robinson","doi":"10.1117/12.2525595","DOIUrl":"https://doi.org/10.1117/12.2525595","url":null,"abstract":"Photodynamic therapy (PDT) has been used clinically for the treatment of head and neck cancer. The effectiveness of PDT is often strongly dependent on fluence rate. Targeted photo-immunotherapy (PIT) may reduce the adverse effects of non-targeted PDT. The in-vivo distribution of the anti-EGFR targeted conjugate Cetuximab-IRDye700DX was investigated. Vascular and tumor responses were determined with respect to fluence rate. \u0000Intra-vital confocal microscopy of skin-fold chambers with the EGFR-overexpressing OSC-19 tumor showed peak tumor fluorescence 24 hrs after administration. Tumor to normal ratio was 3.1±1.6 (n=8). Tumor vascular responses were determined by imaging rhodamine-dextran extravasation. Two hrs after illumination (24 hr DLI, 100 J.cm-2 at 50 mW.cm-2) showed no leakage in 3 of 4 animals and stasis in 1. Normal vasculature showed mild to severe constriction of larger vessels up to 48 hrs after illumination. Subcutaneous OSC-19 tumors were transdermally illuminated with 100 J.cm-2 at 20, 50 and 150 mW.cm-2. Control tumors took 5.3±1.1 days to grow to 200%. All animals treated with 20 mW.cm-2 showed no tumor up to 90 days post treatment (n=4) compared to 1 of 4 in the 50 and 150 mW.cm-2 groups. The remaining tumors reached 200% after 17.9±5.2 and 19.5±7.4 days. Crust formation of the overlying skin was observed at low fluence rate.\u0000Cetuximab-IRDye700DX showed significant tumor to normal ratio. Normal tissue responses like vascular effects and crust formation of the skin was observed and may be caused by conjugate still present in the circulation. The effect of targeted-PIT is strongly dependent on fluence rate.","PeriodicalId":6365,"journal":{"name":"17th International Photodynamic Association World Congress","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80468316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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