title: Comparison of 18F-FES, 18F-FDG, and 18F-FMISO PET Imaging Probes for Early Prediction and Monitoring of Response to Endocrine Therapy in a Mouse Xenograft Model of ER-Positive Breast Cancer.
abstract: BACKGROUND
  There is an increasing need to characterize biological processes for early prediction and monitoring of response to endocrine therapy in breast cancer using multiple positron emission tomography (PET) imaging probes. However, use of more than two PET tracers in a single clinical trial is quite challenging. In this study we carried out a longitudinal investigation of 18F-FES, 18F-FDG, and 18F-FMISO PET imaging probes for early prediction and monitoring of response to endocrine therapy in a mouse xenograft model of estrogen receptor (ER)-positive breast cancer.
  
  
  METHODS
  ER+ human breast cancer ZR-75-1 models were established in female mice that were then randomly assigned to a treatment (fulvestrant, 5.0 mg/week for 21 days) or vehicle group. Micro-PET/CT imaging with 18F-FES, 18F-FDG, and 18F-FMISO was performed on days 0, 3, 14, and 21 after treatment. The uptake value (percentage injected dose per gram, %ID/g) for each probe in tumor (T) tissue and contralateral muscle (M) was measured for quantitative analysis and T/M calculation. Tumor volume was measured to record tumor growth at each time point. Tumor tissues were sampled for immunohistochemical staining of ER expression. Correlations for tumor volume and ERα levels with uptake data for the probe were tested.
  
  
  RESULTS
  Uptake data for 18F-FES in ZR-75-1 tumor tissues corresponded well with tumor response to endocrine therapy, but not for 18F-FDG and 18F-FMISO, according to longitudinal micro-PET/CT imaging and quantitative correlation analysis. There was a significant positive correlation between 18F-FES uptake and ER levels (%ID/gmax r2 = 0.76, P< 0.05; T/M r2 = 0.82, P<0.05). Notably, 18F-FES uptake on day 3 was significantly correlated with the day 21/baseline tumor volume ratio (%ID/gmax r2 = 0.74, P < 0.05; T/M r2 = 0.78, P < 0.05).
  
  
  CONCLUSIONS
  Comparison of 18F-FES, 18F-FDG, and 18F-FMISO probes revealed that 18F-FES PET/CT molecular imaging can provide a precise early prediction of tumor response to endocrine therapy in ER+ breast cancer in a ZR-75-1 xenograft model. This molecular imaging strategy with 18F-FES PET/CT will be useful in evaluating the efficacy of endocrine therapies and in developing new endocrine drugs.
authors.affiliation: Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Center for Biomedical Imaging, Fudan University, Shanghai, China.|Shanghai Engineering Research Center for Molecular Imaging Probes, Shanghai, China.
authors.forename: SiMin
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Center for Biomedical Imaging, Fudan University, Shanghai, China.|Shanghai Engineering Research Center for Molecular Imaging Probes, Shanghai, China.
authors.forename: MingWei
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Center for Biomedical Imaging, Fudan University, Shanghai, China.|Shanghai Engineering Research Center for Molecular Imaging Probes, Shanghai, China.
authors.forename: ZhongYi
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Center for Biomedical Imaging, Fudan University, Shanghai, China.|Shanghai Engineering Research Center for Molecular Imaging Probes, Shanghai, China.
authors.forename: JianPing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Center for Biomedical Imaging, Fudan University, Shanghai, China.|Shanghai Engineering Research Center for Molecular Imaging Probes, Shanghai, China.
authors.forename: YongPing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Center for Biomedical Imaging, Fudan University, Shanghai, China.|Shanghai Engineering Research Center for Molecular Imaging Probes, Shanghai, China.
authors.forename: JianMin
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Center for Biomedical Imaging, Fudan University, Shanghai, China.|Shanghai Engineering Research Center for Molecular Imaging Probes, Shanghai, China.
authors.forename: YingJian
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes / Q000627:therapeutic use*; D064593:Heterografts; D006801:Humans; D051379:Mice; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047628:Estrogen Receptor alpha; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals