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Theranostics 2015; 5(7):698-709. doi:10.7150/thno.11559 This issue Cite

Research Paper

Near Infrared Photoimmunotherapy in the Treatment of Pleural Disseminated NSCLC: Preclinical Experience

Kazuhide Sato, Tadanobu Nagaya, Peter L. Choyke, Hisataka Kobayashi^✉

Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1088.

✉ Corresponding author: Hisataka Kobayashi, MD. PhD. Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, NIH, Building 10, RoomB3B69, MSC1088, Bethesda, MD 20892-1088. Phone: 301-435-4086, Fax: 301-402-3191. E-mail: Kobayashnih.gov. More

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.

Keywords: photoimmunotherapy, fluorescence thoracoscopy, pleural dissemination, bioluminescence imaging, fluorescence imaging.

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