Establishment of a preclinical orthotopic model for human malignant bone disease in immunocompromised NSG mice using small animal PET, CT and MRI imaging


Session type:

Henrike K Knizia1, Mike A Batey1, Gilberto S Almeida1, Ian Wilson1, Ross J Maxwell1, Petra Dildey2, I Geoff Hide2, Chris M Bacon1, H Josef Vormoor1
1Northern Institute for Cancer Research, Newcastle upon Tyne, United Kingdom,2Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom


Ewing sarcoma (ES) and osteosarcoma (OS) are the two most frequent primary osseous sarcomas in childhood and adolescence. In both primary bone tumours and other cancers, bone metastases are the main adverse prognostic factor. Through complex interactions with cells such as osteoblasts and osteoclasts, cancer cells disturb the delicately balanced bone microenvironment causing different patterns of bone remodelling. Orthotopic models are needed both to study the biology of the interaction between tumour cells and bone and as preclinical models for drug development.


To develop a preclinical orthotopic intrafemoral model addressing interaction between tumour and bone, ES cell lines VH-64 and TC-71, OS cell line SaOS-2 and prostate cancer (CaP) cell line PC3M were injected into the right femurs of NSG mice. The disease was tracked using Computed Tomography (CT) and 2-[18F]fluoro-2-deoxy-D-glucose-Positron Emission Tomography (FDG-PET); final Magnetic Resonance Imaging (MRI) documented tumours. Areas of interest identified by imaging were taken for histopathology.


CT images of femurs injected with ES and OS cell lines showed remodelling of the murine bone with induction of pathological new bone formation. Additionally, OS transplanted mice showed formation of new malignant bone within the tumour mass itself. However, CaP cells caused osteolytic lesions and 28% of transplanted mice developed pathological fractures of the injected femur.

Histopathological analysis of the femurs confirmed the findings of CT imaging. Comparison of the model with images and pathology from patients with bone tumours showed a considerable similarity, demonstrating the clinical and biological relevance of the model. Finally, small animal MRI proved to be a good tool to quantify tumour volumes.


We have established a consistent orthotopic xenograft mouse model to study remodelling of the bone microenvironment by malignant cells. Moreover, this model can be used as a quantitative assay for preclinical drug testing.