Won Jun Kang1, Eun Hye Song2, Jun Young Park1, Young Jin Park2, Arthur Cho1, Ho-Taek Song3. 1. Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Korea. 2. Department of Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea. 3. Department of Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea. Electronic address: hotsong@yuhs.ac.
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.
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 humanbreast 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.
Authors: Valerie De Meulenaere; Sara Neyt; Bert Vandeghinste; Pieter Mollet; Olivier De Wever; Elke Decrock; Luc Leybaert; Ingeborg Goethals; Christian Vanhove; Benedicte Descamps; Karel Deblaere Journal: PLoS One Date: 2018-12-10 Impact factor: 3.240