title: Fluence Rate Differences in Photodynamic Therapy Efficacy and Activation of Epidermal Growth Factor Receptor after Treatment of the Tumor-Involved Murine Thoracic Cavity.
abstract: Photodynamic therapy (PDT) of the thoracic cavity can be performed in conjunction with surgery to treat cancers of the lung and its pleura. However, illumination of the cavity results in tissue exposure to a broad range of fluence rates. In a murine model of intrathoracic PDT, we studied the efficacy of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH; Photochlor(®))-mediated PDT in reducing the burden of non-small cell lung cancer for treatments performed at different incident fluence rates (75 versus 150 mW/cm). To better understand a role for growth factor signaling in disease progression after intrathoracic PDT, the expression and activation of epidermal growth factor receptor (EGFR) was evaluated in areas of post-treatment proliferation. The low fluence rate of 75 mW/cm produced the largest reductions in tumor burden. Bioluminescent imaging and histological staining for cell proliferation (anti-Ki-67) identified areas of disease progression at both fluence rates after PDT. However, increased EGFR activation in proliferative areas was detected only after treatment at the higher fluence rate of 150 mW/cm. These data suggest that fluence rate may affect the activation of survival factors, such as EGFR, and weaker activation at lower fluence rate could contribute to a smaller tumor burden after PDT at 75 mW/cm.
authors.affiliation: Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. craig_grossman@urmc.rochester.edu.
authors.forename: Craig E
authors.initials: CE
authors.lastname: Grossman
authors.affiliation: Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. poseysl@mail.med.upenn.edu.
authors.forename: Shirron L
authors.initials: SL
authors.lastname: Carter
authors.affiliation: Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. julie.czupryna@perkinelmer.com.
authors.forename: Julie
authors.initials: J
authors.lastname: Czupryna
authors.affiliation: Department of Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. wangle@mail.med.upenn.edu.
authors.forename: Le
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. mputt@mail.med.upenn.edu.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Putt
authors.affiliation: Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. buschtm@mail.med.upenn.edu.
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Busch
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002734:Chlorophyll / Q000009:adverse effects / Q000031:analogs & derivatives; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D010778:Photochemotherapy / Q000009:adverse effects / Q000379:methods*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism
chemical_list: D001324:Autoantigens; C099558:Ki antigen; D002734:Chlorophyll; C083998:2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a; D066246:ErbB Receptors; D046988:Proteasome Endopeptidase Complex
keywords: HPPH; epidermal growth factor receptor; fluence rate; lung; non-small cell lung carcinoma; optical imaging; photodynamic therapy; proliferation; thoracic cavity