title: Multi-Modal Imaging in a Mouse Model of Orthotopic Lung Cancer.
abstract: BACKGROUND
  Investigation of CF800, a novel PEGylated nano-liposomal imaging agent containing indocyanine green (ICG) and iohexol, for real-time near infrared (NIR) fluorescence and computed tomography (CT) image-guided surgery in an orthotopic lung cancer model in nude mice.
  
  
  METHODS
  CF800 was intravenously administered into 13 mice bearing the H460 orthotopic human lung cancer. At 48 h post-injection (peak imaging agent accumulation time point), ex vivo NIR and CT imaging was performed. A clinical NIR imaging system (SPY®, Novadaq) was used to measure fluorescence intensity of tumor and lung. Tumor-to-background-ratios (TBR) were calculated in inflated and deflated states. The mean Hounsfield unit (HU) of lung tumor was quantified using the CT data set and a semi-automated threshold-based method. Histological evaluation using H&E, the macrophage marker F4/80 and the endothelial cell marker CD31, was performed, and compared to the liposomal fluorescence signal obtained from adjacent tissue sections.
  
  
  RESULTS
  The fluorescence TBR measured when the lung is in the inflated state (2.0 ± 0.58) was significantly greater than in the deflated state (1.42 ± 0.380 (n = 7, p<0.003). Mean fluorescent signal in tumor was highly variable across samples, (49.0 ± 18.8 AU). CT image analysis revealed greater contrast enhancement in lung tumors (a mean increase of 110 ± 57 HU) when CF800 is administered compared to the no contrast enhanced tumors (p = 0.0002).
  
  
  CONCLUSIONS
  Preliminary data suggests that the high fluorescence TBR and CT tumor contrast enhancement provided by CF800 may have clinical utility in localization of lung cancer during CT and NIR image-guided surgery.
authors: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Ontario, Canada.
authors: Priya
authors: P
authors: Patel
authors: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Ontario, Canada.
authors: Tatsuya
authors: T
authors: Kato
authors: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Ontario, Canada.
authors: Hideki
authors: H
authors: Ujiie
authors: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Ontario, Canada.
authors: Hironobu
authors: H
authors: Wada
authors: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Ontario, Canada.
authors: Daiyoon
authors: D
authors: Lee
authors: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Ontario, Canada.
authors: Hsin-Pei
authors: HP
authors: Hu
authors: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Ontario, Canada.
authors: Kentaro
authors: K
authors: Hirohashi
authors: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Ontario, Canada.
authors: Jin Young
authors: JY
authors: Ahn
authors: TECHNA Institute, University Health Network, Ontario, Canada.|Institute of Biomaterials & Biomedical Engineering, University of Toronto, Ontario, Canada.
authors: Jinzi
authors: J
authors: Zheng
authors: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Ontario, Canada.|TECHNA Institute, University Health Network, Ontario, Canada.|Institute of Biomaterials & Biomedical Engineering, University of Toronto, Ontario, Canada.
authors: Kazuhiro
authors: K
authors: Yasufuku
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D021621:Imaging, Three-Dimensional; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D064847:Multimodal Imaging; D061848:Optical Imaging; D014057:Tomography, X-Ray Computed