An orthotopic non-small cell lung cancer model for image-guided small animal radiotherapy platforms

Abstract

Objective: Lung cancer is the deadliest cancer worldwide. To increase treatment potential for lung cancer, pre-clinical models that allow testing and follow up of clinically relevant treatment modalities are essential. Therefore, we developed a single-nodule-based orthotopic non-small cell lung cancer tumor model which can be monitored using multimodal non-invasive imaging to select the optimal image–guided radiation treatment plan. Methods: An orthotopic non-small cell lung cancer model in NMRI-nude mice was established to investigate the complementary information acquired from 80 kVp microcone-beam CT (micro–CBCT) and bioluminescence imaging (BLI) using different angles and filter settings. Different micro–CBCT-based radiation-delivery plans were evaluated based on their dose–volume histogram metrics of tumor and organs at risk to select the optimal treatment plan. Results: H1299 cell suspensions injected directly into the lung render exponentially growing single tumor nodules whose CBCT–based volume quantification strongly correlated with BLI–integrated intensity. Parallel–opposed single angle beam plans through a single lung are preferred for smaller tumors, whereas for larger tumors, plans that spread the radiation dose across healthy tissues are favored. Conclusions: Closely mimicking a clinical setting for lung cancer with highly advanced preclinical radiation treatment planning is possible in mice developing orthotopic lung tumors. Advances in knowledge: BLI and CBCT imaging of orthotopic lung tumors provide complementary information in a temporal manner. The optimal radiotherapy plan is tumor volume-dependent.