METHODS IN MOLECULAR BIOLOGY TM

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1 METHODS IN MOLECULAR BIOLOGY TM Series Editor John M. Walker School of Life Sciences University of Hertfordshire Hatfield, Hertfordshire, AL10 9AB, UK For other titles published in this series, go to

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3 Photodynamic Therapy Methods and Protocols Edited by Charles J. Gomer University of Southern California and Children s Hospital Los Angeles, Los Angeles, CA, USA

4 Editor Charles J. Gomer University of Southern California Keck School of Medicine Children s Hospital Los Angeles 4650 Sunset Blvd. Los Angeles CA USA cgomer@chla.usc.edu ISSN e-issn ISBN e-isbn DOI / Springer New York Dordrecht Heidelberg London Library of Congress Control Number: Springer Science+Business Media, LLC 2010 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Humana Press, c/o Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. While the advice and information in this book are believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Humana Press is part of Springer Science+Business Media (

5 Preface Biological interactions of visible light with photosensitizers have been studied for over a century while controlled clinical applications of light and photosensitizers to treat solid tumors (photodynamic therapy) have been evolving since the mid-1970s. There are hundreds of excellent publications describing basic, preclinical, and clinical applications of PDT for both malignant and non-malignant disorders. However, I believe this book provides the first comprehensive description of methods and protocols specifically related to relevant mechanistic, dosimetric, preclinical, and clinical procedures used in current PDT research. Thinking outside the box is a cliché that seems to garner too much play these days in areas of biomedical science. However, back in the early 1970s, Tom Dougherty, working at Roswell Park, exhibited true out-of-the-box scientific thinking along with a naive determination that successfully brought a totally new therapeutic procedure to the clinic. Tom provides a very interesting and enjoyable history in the introductory chapter of the book on exactly how PDT got its start in his laboratory at Roswell Park. As Tom s first graduate student, I was fortunate to be working in his laboratory during that exciting time period. During those early days of PDT-directed research, it was assumed that when cells were exposed to a photosensitizer, porphyrin derivatives being among the most often used, and visible light, that photochemically generated reactive oxygen species killed these cells by simply damaging cell membranes and/or vital subcellular structures. This certainly plays a role in PDT-mediated cell kill, but as is clearly observed and described in this book, numerous signal transduction and cell death pathways are also involved. The in vivo situation is even more complex. A growing number of studies are demonstrating that immunological, tumor microenvironmental, and vascular responses are all contributing to PDT treatment outcomes. Photophysical methods to monitor treatment responses are now providing realtime analysis of PDT doses and PDT efficacy. Finally, effective clinical trials remain the primary long-term objective of all PDT research. A variety of PDT applications for both malignant and non-malignant diseases and disorders are now showing promise. The goal of this book is to provide the reader with current and useful protocols that can be used to evaluate mechanisms and applications of PDT. Leading PDT scientists and clinicians have contributed to this book by providing chapters with clear roadmaps, methodologies, and suggestions that should prove beneficial to new investigators just starting out in PDT research as well as seasoned investigators changing the direction of their research. I would like to thank all of the contributors of this book for their efforts, enthusiasm, and patience. I also want to thank John Walker, Series Editor, for his consistent encouragement and assistance. Charles J. Gomer v

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7 Contents Preface... v Contributors... ix 1. Introduction... 1 Thomas J. Dougherty 2. Death and Survival Signals in Photodynamic Therapy... 7 Michael Dewaele, Tom Verfaillie, Wim Martinet, and Patrizia Agostinis 3. Photodynamic Therapy and Cell Death Pathways David Kessel and Nancy L. Oleinick 4. Identification of MAP Kinase Pathways Involved in COX-2 Expression Following Photofrin Photodynamic Therapy Marian Luna, Angela Ferrario, Sam Wong, and Charles J. Gomer 5. Metronomic PDT and Cell Death Pathways Gurmit Singh, Omar Alqawi, and Myrna Espiritu 6. How to Monitor NF-κB Activation After Photodynamic Therapy Isabelle Coupienne, Jacques Piette, and Sébastien Bontems 7. Application of 5-Aminolevulinic Acid and Its Derivatives for Photodynamic Therapy In Vitro and In Vivo Asta Juzeniene, Petras Juzenas, and Johan Moan 8. Hypoxia and Perfusion Labeling During Photodynamic Therapy Theresa M. Busch 9. Targeting the Tumor Microenvironment Using Photodynamic Therapy Combined with Inhibitors of Cyclooxygenase-2 or Vascular Endothelial Growth Factor Angela Ferrario and Charles J. Gomer 10. Photochemical Internalization (PCI): A Technology for Drug Delivery Kristian Berg, Anette Weyergang, Lina Prasmickaite, Anette Bonsted, Anders Høgset, Marie-Therese R. Strand, Ernst Wagner, and Pål K. Selbo 11. Photodynamic Therapy-Generated Cancer Vaccines Mladen Korbelik 12. Antimicrobial Photodynamic Inactivation and Photodynamic Therapy for Infections Liyi Huang, Tianhong Dai, and Michael R. Hamblin 13. Photodynamic Therapy of Bacterial and Fungal Biofilm Infections Merrill A. Biel vii

8 viii Contents 14. Calculation of Cellular Oxygen Concentration for Photodynamic Therapy In Vitro Michael S. Patterson and Emma Mazurek 15. Fluorescent Molecular Imaging and Dosimetry Tools in Photodynamic Therapy Brian W. Pogue, Kimberley S. Samkoe, Summer L. Gibbs-Strauss, and Scott C. Davis 16. Bifunctional Agents for Imaging and Therapy Ravindra K. Pandey, Nadine S. James, Yihui Chen, Joseph Missert, and Munawar Sajjad 17. Photodynamic Diagnosis and Therapy and the Brain Herwig Kostron 18. Photodynamic Therapy of Head and Neck Cancers Merrill A. Biel Subject Index

9 Contributors PATRIZIA AGOSTINIS Department of Molecular and Cell Biology, Catholic University of Leuven, Leuven, Belgium OMAR ALQAWI Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada KRISTIAN BERG Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo, Norway MERRILL A. BIEL Virginia Piper Cancer Institute, Minneapolis, MN; Department of Otolaryngology, Surgery and Family Practice, University of Minnesota, Minneapolis, MN, USA ANETTE BONSTED Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo, Norway SÉBASTIEN BONTEMS Laboratory of Virology and Immunology, GIGA-R, B34 +2, CHU, Liege, Belgium THERESA M. BUSCH Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA YIHUI CHEN PDT Center, Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY; Department of Nuclear Chemistry, SUNY, Buffalo, NY, USA ISABELLE COUPIENNE Laboratory of Virology and Immunology, GIGA-R, B34 +2, CHU, Liege, Belgium TIANHONG DAI Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA; Department of Dermatology, Harvard Medical School, Boston, MA, USA SCOTT C. DAVIS Thayer School of Engineering, Dartmouth College, Hanover, NH, USA MICHAEL DEWAELE Department of Molecular and Cell Biology, Catholic University of Leuven, Leuven, Belgium THOMAS J. DOUGHERTY Roswell Park Cancer Institute, Buffalo, NY, USA MYRNA ESPIRITU Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada ANGELA FERRARIO The Saban Research Institute, Children s Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA SUMMER L. GIBBS-STRAUSS Thayer School of Engineering, Dartmouth College, Hanover, NH, USA ix

10 x Contributors CHARLES J. GOMER Departments of Pediatrics and Radiation Oncology, Keck School of Medicine, The Saban Research Institute, Children s Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA MICHAEL R. HAMBLIN Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA; Department of Dermatology, Harvard Medical School, Boston, MA; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA ANDERS HØGSET PCI Biotech AS, Oslo, Norway LIYI HUANG Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA; Department of Dermatology, Harvard Medical School, Boston, MA, USA; Department of Infectious Diseases, First Affiliated College & Hospital, Guangxi Medical University, Nanning, China NADINE S. JAMES PDT Center, Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA PETRAS JUZENAS Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo, Norway ASTA JUZENIENE Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo, Norway DAVID KESSEL Wayne State University School of Medicine, Detroit, MI, USA MLADEN KORBELIK B.C. Cancer Agency, Vancouver, BC, Canada HERWIG KOSTRON Department of Neurosurgery, Medical University of Innsbruck, Innsbruck, Austria MARIAN LUNA The Saban Research Institute, Children s Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA WIM MARTINET Division of Pharmacology, University of Antwerp, Antwerp, Belgium EMMA MAZUREK Juravinski Cancer Centre and McMaster University, Hamilton, ON, Canada JOSEPH MISSERT PDT Center, Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA JOHAN MOAN Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo, Norway; Institute of Physics, University of Oslo, Oslo, Norway NANCY L. OLEINICK Case Western Reserve University, Cleveland, OH, USA RAVINDRA K. PANDEY PDT Center, Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA MICHAEL S. PATTERSON Juravinski Cancer Centre and McMaster University, Hamilton, ON, Canada JACQUES PIETTE Laboratory of Virology and Immunology, GIGA-R, B34 +2, CHU, Liege, Belgium

11 Contributors xi BRIAN W. POGUE Thayer School of Engineering, Dartmouth College, Hanover, NH, USA LINA PRASMICKAITE Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo, Norway MUNAWAR SAJJAD PDT Center, Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY; Department of Nuclear Chemistry, SUNY, Buffalo, NY, USA KIMBERLEY S. SAMKOE Thayer School of Engineering, Dartmouth College, Hanover, NH, USA PÅL K. SELBO Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo, Norway GURMIT SINGH Department of Pathology and Molecular Medicine, Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada MARIE-THERESE R. STRAND Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo, Norway TOM VERFAILLIE Department of Molecular and Cell Biology, Catholic University of Leuven, Leuven, Belgium ERNST WAGNER Pharmaceutical Biology-Biotechnology, Department of Pharmacy, Ludwig-Maximilians-Universitaet, Munich, Germany ANETTE WEYERGANG Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo, Norway SAM WONG The Saban Research Institute, Southern California, Los Angeles, CA, USA Children s Hospital Los Angeles, University of