title: Near infrared photoimmunotherapy for lung metastases.
abstract: Lung metastases are a leading cause of cancer related deaths; nonetheless current treatments are limited. Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of intravenously injected antibodies that target tumors with the toxicity induced by photosensitizers activated by NIR-light. Herein, we demonstrate the efficacy of NIR-PIT in a mouse model of lung metastases. Experiments were conducted with a HER2, luciferase and GFP expressing cell line (3T3/HER2-luc-GFP). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye700DX, was synthesized. In vitro NIR-PIT-induced cytotoxicity was light dose dependent. With 3D culture, repeated NIR-PIT could eradicate entire spheroids. In vivo anti-tumor effects of NIR-PIT included significant reductions in both tumor volume (p = 0.0141 vs. APC) and bioluminescence image (BLI) (p = 0.0086 vs. APC) in the flank model, and prolonged survival (p < 0.0001). BLI demonstrated a significant reduction in lung metastases volume (p = 0.0117 vs. APC). Multiple NIR-PIT doses significantly prolonged survival in the lung metastasis model (p < 0.0001). These results suggested that NIR-PIT is a potential new therapy for the local control of lung metastases.
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Sato
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Tadanobu
authors.initials: T
authors.lastname: Nagaya
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Makoto
authors.initials: M
authors.lastname: Mitsunaga
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. Electronic address: Kobayash@mail.nih.gov.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D041702:BALB 3T3 Cells; D004305:Dose-Response Relationship, Drug; D005260:Female; D017930:Genes, Reporter; D007167:Immunotherapy / Q000379:methods*; D007211:Indoles / Q000494:pharmacology*; D054833:Isoindoles; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000556:secondary* / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D017319:Photosensitizing Agents / Q000494:pharmacology*; D010789:Phototherapy / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014162:Transfection; D000068878:Trastuzumab; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007211:Indoles; D054833:Isoindoles; D008164:Luminescent Proteins; D017319:Photosensitizing Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C013647:phthalocyanine
keywords: Bioluminescence; HER2 receptor; Lung metastases; Near infrared photoimmunotherapy