Improvement of orthotopic lung cancer mouse model via thoracotomy and orotracheal intubation enabling in vivo imaging studies

Investigation of molecular mechanisms and the efficiency of novel therapeutics for the treatment and prevention of a disease require accurate and accessible preclinical models. Recent developments in personalized medicine employing molecular medicine concepts have favored mice because their genetic make-up is well known and easy to manipulate. For lung cancer, however, orthotopic models in mice are difficult to create due to their narrow glottis openings which act as obstacles to intubation. In the present study, we develop an orotracheal intubation device which gives a clearer view of the narrow mouse glottis and increases the success rate of intubation. We achieved anesthetization via orotracheal intubation using this novel device and then performed a thoracotomy by making an incision between the fourth and fifth intercostal ribs on the right side of the chest. Lung tumor cells were then inoculated at this site. Tumor formation was monitored through bioluminescence optical and magnetic resonance (MR) imagings, which was confirmed by histological analysis. Temperature drop (<35°C) and/or loss of body weight (>30% of the initial body weight) observed during any procedure were used as interruption criteria. This method exhibited high tumorigenicity (100%) and a low mortality rate (8%) at specific sites making it ideal for creating orthotopic lung tumor models and making it particularly useful for sequential follow-up studies using in vivo image analysis.