title: Near infrared photoimmunotherapy in the treatment of pleural disseminated NSCLC: preclinical experience.
abstract: Pleural metastases are common in patients with advanced thoracic cancers and are a cause of considerable morbidity and mortality yet is difficult to treat. Near Infrared Photoimmunotherapy (NIR-PIT) is a cancer treatment that combines the specificity of intravenously injected antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to NIR-light. Herein, we evaluate the efficacy of NIR-PIT in a mouse model of pleural disseminated non-small cell lung carcinoma (NSCLC). In vitro and in vivo experiments were conducted with a HER2, luciferase and GFP expressing NSCLC cell line (Calu3-luc-GFP). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye-700DX, was synthesized. In vitro NIR-PIT cytotoxicity was assessed with dead staining, luciferase activity, and GFP fluorescence intensity. In vivo NIR-PIT was performed in mice with tumors implanted intrathoracic cavity or in the flank, and assessed by tumor volume and/or bioluminescence and fluorescence thoracoscopy. In vitro NIR-PIT-induced cytotoxicity was light dose dependent. In vivo NIR-PIT led significant reductions in both tumor volume (p = 0.002 vs. APC) and luciferase activity (p = 0.0004 vs. APC) in a flank model, and prolonged survival (p < 0.0001). Bioluminescence indicated that NIR-PIT lead to significant reduction in pleural dissemination (1 day after PIT; p = 0.0180). Fluorescence thoracoscopy confirmed the NIR-PIT effect on disseminated pleural disease. In conclusion, NIR-PIT has the ability to effectively treat pleural metastases caused by NSCLC in mice. Thus, NIR-PIT is a promising therapy for pleural disseminated tumors.
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1088.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Sato
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1088.
authors.forename: Tadanobu
authors.initials: T
authors.lastname: Nagaya
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1088.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1088.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D005456:Fluorescent Dyes; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007259:Infrared Rays; D051379:Mice; D010778:Photochemotherapy / Q000379:methods*; D016066:Pleural Effusion, Malignant / Q000628:therapy*; D000068878:Trastuzumab / Q000627:therapeutic use
chemical_list: D005456:Fluorescent Dyes; D000068878:Trastuzumab
keywords: bioluminescence imaging; fluorescence imaging.; fluorescence thoracoscopy; photoimmunotherapy; pleural dissemination