Development of a peripheral lung cancer model in rabbits using thoracoscopic-guided bronchoscopic inoculation

In preclinical research, tumor models are most commonly established by direct inoculation of tumor cell suspensions into the target organ. In the lung, however, precise delivery to a designated site is technically difficult, and leakage of cells into adjacent tissues such as the pleural cavity may cause diffuse spread rather than localized tumor formation. A model that reproducibly forms a tumor at a predetermined peripheral location would provide a useful experimental platform for studies on surgical approaches or stereotactic body radiation therapy (SBRT). This study aimed to develop such a peripheral lung cancer model in rabbits.

New Zealand White rabbits were anesthetized with intramuscular ketamine and xylazine, intubated, and maintained on sevoflurane. A flexible bronchoscope (3.7-mm outer diameter) was advanced to the orifice of the lateral segment of the right lower lobe, and a 1-mm Teflon catheter was passed through its working channel into the segmental bronchus under direct vision. Through a small intercostal incision, a thoracoscope was introduced, and the parenchymal site corresponding to the catheter tip was identified. Under thoracoscopic guidance, a VX2 tumor cell suspension, alone or mixed with lipiodol, was injected through the catheter. Tumor progression was monitored by serial chest radiography at 2 and 4 weeks. At week 5, the animals were euthanized, and the trachea and right lung were resected en bloc for histopathological analysis.

Tumor formation was observed in six rabbits. Among animals given the optimized protocol (larger rabbits injected with the VX2-lipiodol mixture), four of five developed pulmonary tumors and three showed tumors localized to the intended peripheral region, whereas tumors induced with VX2 alone grew invasively without peripheral localization. Histopathological examination confirmed malignancy at the target site.

Thoracoscopy-guided bronchoscopic inoculation, particularly when combined with lipiodol, enabled localized establishment of peripheral lung tumors in rabbits. The model provides a basis for developing preclinical platforms to evaluate diagnostic modalities and localized therapies such as SBRT, although further refinement and validation are required.