Evaluation of oxygen dependence on in vitro and in vivo cytotoxicity of photoimmunotherapy using IR-700–antibody conjugates |
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| Institution: | 1. Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA;2. Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA;3. Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, Building 10, Room B3B69, NIH, 10 Center Drive, Bethesda, MD 20892-1002, USA;1. Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan;2. Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan;3. Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan;1. M.V. Lomonosov Moscow State University of Fine Chemical Technologies, Prospect Vernadskogo, 86, 119571, Moscow, Russia;2. N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect, 47, 119991, Moscow, Russia;3. A.N. Bach Institute of Biochemistry, Russian Academy of Sciences, Leninsky Prospect, 33, 119071, Moscow, Russia;4. A.V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences, Leninsky Prospect, 29, 119991, Moscow, Russia;5. Institute for Physical-Chemical Medicine, Malaya Pirogovskaya St., 1a, 119828, Moscow, Russia;1. Department of Chemistry, Hunter College of the City University of New York, 695 Park Avenue, New York, NY 10065, United States;2. Department of Natural Sciences, LaGuardia Community College of the City University of New York, 31-10 Thomson Avenue, Long Island City, New York, NY 11101, United States;3. Department of Molecular and Cellular Physiology and Department of Ophthalmology, Albany Medical College, Albany, NY 12208, United States;4. Centro de Química Estrutural, Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal;1. Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands;2. Membrane Biochemistry and Biophysics, Institute of Biomembranes, University of Utrecht, Padualaan 8, 3584 CH Utrecht, The Netherlands;3. Department of Gastroenterology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands;1. Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China;2. Division of Medical Sciences, Weifang People''s Hospital, Weifang 261000, China;3. Interdisciplinary Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China |
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| Abstract: | Photoimmunotherapy (PIT) using the near-infrared-absorbing photosensitizing phthalocyanine dye, IRDye 700DX (IR-700), conjugated with a tumor-targeting antibody such as panitumumab (Pan) has shown efficacy in in vitro studies and several preclinical models in mice with promise for clinical translation. PIT results in rapid necrotic cell death in vitro and tumor shrinkage in vivo. Photochemical studies with the Pan-IR-700 conjugate showed that this agent can support generation of singlet oxygen and also generate reactive oxygen species after exposure to near-infrared (NIR) light. Moreover, in vitro studies using A431 cells, singlet oxygen scavengers abrogated the efficacy of PIT with Pan-IR-700, while oxygen depletion to undetectable levels in the exposure chamber almost completely inhibited the cellular cytotoxicity of PIT. Survival of tumor bearing mice was prolonged in PIT-treated animals but mice whose tumors were made transiently hypoxic prior to PIT had no benefit from the treatment. The results from this study support a central role for molecular oxygen-derived species in cell death caused by PIT. |
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| Keywords: | Photodynamic therapy Photoimmunotherapy Singlet oxygen ROS Hypoxia |
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