Comparison of F-18 FDG and F-18 Fluoride PET imaging in bone metastasis from breast cancer rat model

Abstract

Adequate animal disease model and its evaluation method are crucial in developing therapeutic agents. We designed a rat model of bone metastasis and in vivo imaging system with microPET. Methods: Human breast cancer cell line (MDA-MB231) trasfected with luciferase gene was injected into left ventricle of nude rat under ultrasonographic guidance. Bioluminescence imaging was performed to confirm development of bone metastasis. MicroPET scans using F-18 FDG and F-18 fluoride were acquired longitudinally up to 4 week. Bioluminescence imaging, F-18 FDG, and F-18 fluoride PET images were compared with histopathologic results in the same rat. Results: Bioluminescence image validated successful development of bone metastasis by showing bioluminescence signal on bilateral hind limb and spines. Bioluminescence signal increased gradually up to 4 week indicating disease progression. F-18 FDG PET revealed increased FDG uptake on bilateral hind limb and spines at 2 week images, and showed progressive pattern up to 4 week. F-18 fluoride PET showed minimal abnormal findings at 2 week images, but it showed irregular pattern at spine from 3 or 4 week images. On quantitative analysis with standardized uptake value (SUV), gradual increase pattern was observed from 2 weeks to 4 weeks both in FDG PET and fluoride PET. Histopathologic exam confirmd the formation of osteolytic metastasis at femur, which were compatibe with image findings. Conclusion: Orthotopic breast cancer bone metastasis model in nude rat could be visualized by animal PET. Nude rat model with animal PET imaging could facilitate the evaluation of therapeutic response by new therapeutic regimen.