title: [18F]-fluoroestradiol quantitative PET imaging to differentiate ER+ and ERα-knockdown breast tumors in mice.
abstract: BACKGROUND
  The purpose of this study was to develop a noninvasive model in tumor-bearing mice to investigate the use of 16α-[(18)F]fluoro-17β-estradiol (FES) positron emission tomography (PET) imaging as a tool to discriminate between tumors having different estrogen receptor (ER) α status.
  
  
  METHODS
  MC7-L1 and MC4-L2 murine mammary adenocarcinoma cell lines (ER+) received a small hairpin RNA targeting the ERα gene by lentiviral infection. In vitro assessment of ERα levels of the new cell lines (MC7-L1 and MC4-L2 ERα-knockdown; ERαKD), compared to the parental cell lines, was performed by immunoblotting (-75% ERα protein) and binding assays (-50% estrogen binding). These cell lines were implanted subcutaneously in Balb/c mice and allowed to grow up to a volume of at least 20 mm(3). FES and [(18)F]fluorodeoxyglucose (FDG) PET images were acquired to measure FES and FDG uptake in the various tumors.
  
  
  RESULTS
  FES uptake as assessed by PET imaging was 1.06±0.21 percent injected dose per gram of tissue (%ID/g) for MC7-L1 tumors and 0.47±0.08 %ID/g for MC7-L1 ERαKD tumors. MC4-L2 tumors had a FES uptake of 1.03±0.30 %ID/g, whereas its ERαKD equivalent was 0.51±0.19 %ID/g. Each ERαKD tumor had a significantly lower %ID/g value, by ~50%, than its ER+ counterpart. Biodistribution studies confirmed these findings and gave %ID/g values that were not significantly different from PET imaging data. FDG PET showed no significant uptake difference between the ER+ and ERαKD tumors, indicating that the metabolic phenotype of the ERαKD cell lines was not altered.
  
  
  CONCLUSIONS
  FES PET imaging was able to reliably differentiate between tumors having differences in their ERα expression in vivo, in a mouse model. Quantitative data obtained by FES PET were in concordance with biodistribution studies and in vitro assays. It is concluded that FES PET imaging can likely be used to monitor subtle ER status changes during the course of hormone therapy.
authors.affiliation: Sherbrooke Molecular Imaging Center, Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4.
authors.forename: Michel
authors.initials: M
authors.lastname: Paquette
authors.forename: René
authors.initials: R
authors.lastname: Ouellet
authors.forename: Mélanie
authors.initials: M
authors.lastname: Archambault
authors.forename: Étienne
authors.initials: É
authors.lastname: Croteau
authors.forename: Roger
authors.initials: R
authors.lastname: Lecomte
authors.forename: François
authors.initials: F
authors.lastname: Bénard
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000235:genetics; D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics; D045744:Cell Line, Tumor; D004958:Estradiol; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens; D005260:Female; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D011960:Receptors, Estrogen; D019788:Fluorodeoxyglucose F18; D004958:Estradiol