title: Evaluation of oxygen dependence on in vitro and in vivo cytotoxicity of photoimmunotherapy using IR-700-antibody conjugates.
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.
authors: Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Shun
authors: S
authors: Kishimoto
authors: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Marcelino
authors: M
authors: Bernardo
authors: Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Keita
authors: K
authors: Saito
authors: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Sho
authors: S
authors: Koyasu
authors: Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: James B
authors: JB
authors: Mitchell
authors: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Peter L
authors: PL
authors: Choyke
authors: Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, Building 10, Room B3B69, NIH, 10 Center Drive, Bethesda, MD 20892-1002, USA. Electronic address: murali@helix.nih.gov.
authors: Murali C
authors: MC
authors: Krishna
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D018796:Immunoconjugates / Q000633:toxicity*; D007167:Immunotherapy; D066298:In Vitro Techniques; D007211:Indoles / Q000633:toxicity*; D054833:Isoindoles; D051379:Mice; D008819:Mice, Nude; D010100:Oxygen / Q000378:metabolism; D017319:Photosensitizing Agents / Q000633:toxicity*; D010789:Phototherapy; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D018796:Immunoconjugates; D007211:Indoles; D054833:Isoindoles; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D010100:Oxygen; C013647:phthalocyanine
keywords: Hypoxia; Photodynamic therapy; Photoimmunotherapy; ROS; Singlet oxygen