【Abstract】 Objective To establish a mouse model bearing human prostate cancer xenograft with bone metastasis by the monitoring with X-Ray, Micro CT, and 18F-NaF PET/CT. Methods Sixteen male Balb/c nude mice were allocated into control (6 mice) and experimental group (10 mice). In experimental group, the mice were subjected to percutaneous injection of 2×105PC-3 cells into tibial plateau, bone defects were assessed after 21 d by X-ray, Micro-CT and 18F-NaF PET/CT, and bone damages were evaluated by HE staining. In control group, equal volume of saline was injected into the mice. Results At 21 d post modeling, the significant radioactive 18F-NaF signals were found in the tibial intramedullary cavity of all 10 mice in experimental group. The ROI value evaluation showed that SUVmaxin control group was 0.62±0.14, but SUVmaxin tumor group was 2.10±0.13,which indicated abnormal bone metabolism. The serum alkaline phosphate level and HE staining results also confirmed that tumor mediated bone destruction and osteogenesis. However, X-ray and Micro-CT did not indicate precise diagnostic bone defect. Conclusion Bone metastasis model of prostate PC-3 cancer cells were successfully established by intratibial injection. 18F-NaF PET/CT could detect tumor invasion and bone osteogenesis in the early stage of modeling.