title: Immediate in vivo target-specific cancer cell death after near infrared photoimmunotherapy.
abstract: BACKGROUND
  Near infrared (NIR) photoimmunotherapy (PIT) is a new type of cancer treatment based on a monoclonal antibody (mAb)-NIR phthalocyanine dye, (IR700) conjugate. In vitro cancer-specific cell death occurs during NIR light exposure in cells previously incubated with mAb-IR700 conjugates. However, documenting rapid cell death in vivo is more difficult.
  
  
  METHODS
  A luciferase-transfected breast cancer cell (epidermal growth factor receptor+, MDA-MB-468luc cells) was produced and used for both in vitro and in vivo experiments for monitoring the cell killing effect of PIT. After validation of cytotoxicity with NIR exposure up to 8 J/cm2in vitro, we employed an orthotopic breast cancer model of bilateral MDA-MB-468luc tumors in female athymic mice, which subsequently received a panitumumab-IR700 conjugate in vivo. One side was used as a control, while the other was treated with NIR light of dose ranging from 50 to 150 J/cm2. Bioluminescence imaging (BLI) was performed before and after PIT.
  
  
  RESULTS
  Dose-dependent cell killing and regrowth was successfully monitored by the BLI signal in vitro. Although tumor sizes were unchanged, BLI signals decreased by >95% immediately after PIT in vivo when light intensity was high (>100 J/cm2), however, in mice receiving lower intensity NIR (50 J/cm2), tumors recurred with gradually increasing BLI signal.
  
  
  CONCLUSIONS
  PIT induced massive cell death of targeted tumor cells immediately after exposure of NIR light that was demonstrated with BLI in vivo.
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room B3B69, MSC1088, Bethesda, MD 20892-1088, USA.
authors.forename: Makoto
authors.initials: M
authors.lastname: Mitsunaga
authors.forename: Takahito
authors.initials: T
authors.lastname: Nakajima
authors.forename: Kohei
authors.initials: K
authors.lastname: Sano
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kramer-Marek
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology*; D007167:Immunotherapy / Q000379:methods*; D007211:Indoles / Q000494:pharmacology*; D054833:Isoindoles; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009336:Necrosis; D000077544:Panitumumab; D010778:Photochemotherapy / Q000379:methods*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D011897:Random Allocation; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018796:Immunoconjugates; D007211:Indoles; D054833:Isoindoles; D011838:Radiation-Sensitizing Agents; D000077544:Panitumumab; D066246:ErbB Receptors; C013647:phthalocyanine