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The aims of these studies were to establish an orthotopic non-small-cell lung cancer (NSCLC) mouse model and to investigate the therapeutic efficacy of lipid-based nanoparticles (NPs) containing 2′-(2-bromohexadecanoyl)-docetaxel (Br-C16-DX) in this new model. A novel orthotopic NSCLC model was established in nude mice through a dorsal side injection of luciferase-expressing A549 cells. The model was characterized by a survival study, histological staining, bioluminescence imaging and PET/CT imaging. The therapeutic efficacy of the Br-C16-DX NPs versus Taxotere® was investigated in this model. The results demonstrated that mouse survival time was significantly prolonged by weekly intravenous administration of the NPs or Taxotere. Furthermore, the NP group had 35 days longer progression-free survival and 27 days longer median survival compared to the Taxotere group. It was concluded that …