(18)F-fluoride PET imaging in a nude rat model of bone metastasis from breast cancer: Comparison with (18)F-FDG and bioluminescence imaging

Abstract

INTRODUCTION: Clinically-relevant animal models and appropriate imaging diagnostic tools are essential to study cancer and develop novel therapeutics. We evaluated a model of bone metastasis in nude rats by micro-PET and bioluminescence imaging. METHODS: A bone metastasis model was produced by intracardiac injection of osteotropic MDA-MB-231Bo-Luc human breast cancer cells into nude rats. Bioluminescence imaging and micro-PET scans using (18)F-FDG and (18)F-fluoride were acquired serially for 5 weeks. We correlated bioluminescence imaging, (18)F-FDG and (18)F-fluoride PET images, and histological slides. RESULTS: Multiple bone metastases were successfully evaluated by bioluminescence imaging and (18)F-FDG and (18)F-fluoride PET scans. Bioluminescence photon flux increased exponentially on weekly follow-up. (18)F-FDG PET revealed increased FDG uptake at the spine and bilaterally in the hind legs in week 2 images, and showed a progressive pattern up to 4 weeks that correlated with bioluminescence imaging. (18)F-fluoride PET showed minimal abnormal findings in week 2 images, but it showed an irregular pattern at the spine from week 3 or 4 images. On quantitative analysis with standardized uptake values, a pattern of gradual increase was observed from week 2 to week 4 in both (18)F-FDG PET and fluoride PET. Histopathological examination confirmed the formation of osteolytic metastasis and necrosis of the distal femur, which appeared as a photon defect on PET scans. CONCLUSION: Developing bone metastasis from breast cancer in a nude rat model was successfully evaluated with an animal PET imaging system and bioluminescence imaging. This nude rat model of bone metastasis, which can be evaluated by PET imaging, may be a valuable tool for evaluating early responses to novel therapeutics.