title: A novel minimally invasive technique to create a rabbit VX2 lung tumor model for nano-sized image contrast and interventional studies.
abstract: BACKGROUND
  The rabbit VX2 lung cancer model is a large animal model useful for preclinical lung cancer imaging and interventional studies. However, previously reported models had issues in terms of invasiveness of tumor inoculation, control of tumor aggressiveness and incidence of complications.
  
  
  OBJECTIVE
  We aimed to develop a minimally invasive rabbit VX2 lung cancer model suitable for imaging and transbronchial interventional studies.
  
  
  METHODS
  New Zealand white rabbits and VX2 tumors were used in the study. An ultra-thin bronchoscope was inserted through a miniature laryngeal mask airway into the bronchus. Different numbers of VX2 tumor cells were selectively inoculated into the lung parenchyma or subcarinal mediastinum to create a uniform tumor with low incidence of complications. The model was characterized by CT, FDG-PET, and endobronchial ultrasound (EBUS). Liposomal dual-modality contrast agent was used to evaluate liposome drug delivery system in this model.
  
  
  RESULTS
  Both peripheral and mediastinal lung tumor models were created. The tumor making success rate was 75.8% (25/33) in the peripheral lung tumor model and 60% (3/5) in the mediastinal tumor model. The group of 1.0×10(6) of VX2 tumor cells inoculation showed a linear growth curve with less incidence of complications. Radial probe EBUS visualized the internal structure of the tumor and the size measurement correlated well with CT measurements (r(2) = 0.98). Over 7 days of continuous enhancement of the lung tumor by liposomal contrast in the lung tumor was confirmed both CT and fluorescence imaging.
  
  
  CONCLUSIONS
  Our minimally invasive bronchoscopic rabbit VX2 lung cancer model is an ideal platform for lung cancer imaging and preclinical bronchoscopic interventional studies.
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Toronto General Hospital, University of Toronto, University Health Network, Toronto, Canada.
authors.forename: Takashi
authors.initials: T
authors.lastname: Anayama
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakajima
authors.forename: Michael
authors.initials: M
authors.lastname: Dunne
authors.forename: Jinzi
authors.initials: J
authors.lastname: Zheng
authors.forename: Christine
authors.initials: C
authors.lastname: Allen
authors.forename: Brandon
authors.initials: B
authors.lastname: Driscoll
authors.forename: Douglass
authors.initials: D
authors.lastname: Vines
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
authors.forename: David
authors.initials: D
authors.lastname: Jaffray
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yasufuku
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000473:pathology; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000008:administration & dosage; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007472:Iohexol / Q000008:administration & dosage; D008081:Liposomes; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D053769:Nanocapsules; D009368:Neoplasm Transplantation; D061848:Optical Imaging; D010316:Particle Size; D011817:Rabbits; D011877:Radionuclide Imaging; D047368:Tumor Burden; D055114:X-Ray Microtomography
chemical_list: D003287:Contrast Media; D008081:Liposomes; D053769:Nanocapsules; D019788:Fluorodeoxyglucose F18; D007472:Iohexol