SESSION TYPE: Biomarkers, Oncogenes and Enhanced Bronchoscopy in NSCLC
PRESENTED ON: Wednesday, October 24, 2012 at 02:45 PM - 04:15 PM
PURPOSE: Recent advances in bronchoscopy such as autofluorescence imaging are useful for detecting early lung cancer (carcinoma in-situ) within the bronchial mucosa. The alternative, to use targeted exogenous fluorophores, has been little explored. Recently discovered multifunctional organic nanoparticles, “Porphysomes”, will accumulate in neoplastic lesions because of the EPR effect. Here, endoscopic lung cancer visualization was examined in orthotopic lung cancer animal models using a prototype bronchoscope designed for imaging near-infrared porphysome fluorescence.
METHODS: A rabbit VX2 orthotopic lung cancer model and nude mouse orthotopic human lung cancer A549 xenograft model were used. Porphysomes were administrated intravenously at a dose of 10 - 30 mg kg-1. Systemic biodistribution and accumulation of the fluorophore in the tumour was analysed in vivo using a small-animal, whole-body imager. The endoscopic field of view was excited with a 650-670nm / 10mW diode light source via the illumination channels and emission light was filtered with a 678nm long pass filter. Fluorescence was recorded using a CCD camera attached to the ocular lens of a bronchofiberscope.
RESULTS: In an in-vitro setting, the prototype fluorescent bronchoscope system could detect the bright fluorescence of the porphysome with a 50uM or higher concentration. In-vivo imaging revealed that the porphysomes accumulate in the orthotopic lung cancers in rabbits and mice, using a 200 ms exposure time, which is compatible with clinical bronchoscopic examination. Ex-vivo studies show that in addition to superficial lesions, porphysome fluorescence from tumours overlaid by a bronchial wall or lung parenchyma 2mm thick was detected by the system.
CONCLUSIONS: Intravenously administrated porphysome nanoparticles successfully accumulated in the orthotopic lung cancers, and the near-infrared nanoparticle fluorescence was successfully detected with a prototype fluorescent endoscope.
CLINICAL IMPLICATIONS: These studies provide promising data to support the technical feasibility of bronchoscopic fluorescence visualization of lung cancers with systemic porphysome administration.
DISCLOSURE: The following authors have nothing to disclose: Takashi Anayama, Patrick McVeigh, Cheng Jin, Takahiro Nakajima, Brian Wilson, Gang Zheng, Shaf Keshavjee, Kazuhiro Yasufuku
We will discuss about our system which is consisted of prototype optical lens changer, CCD camera, diode light source, and bronchofiberscope.Latner Thoracic Surgery Research Laboratory, Division of Thoracic Surgery, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, ON, Canada