title: (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: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Won Jun
authors.initials: WJ
authors.lastname: Kang
authors.affiliation: Department of Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Eun Hye
authors.initials: EH
authors.lastname: Song
authors.affiliation: Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Park
authors.affiliation: Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Arthur
authors.initials: A
authors.lastname: Cho
authors.affiliation: Department of Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Korea. Electronic address: hotsong@yuhs.ac.
authors.forename: Ho-Taek
authors.initials: HT
authors.lastname: Song
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000000981:diagnostic imaging* / Q000556:secondary*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D008163:Luminescent Measurements / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D051381:Rats; D011923:Rats, Nude; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: (18)F-fluoride PET; Bone metastasis; Breast cancer; FDG PET; Nude rat model