title: Assessment of the novel estrogen receptor PET tracer 4-fluoro-11β-methoxy-16α-[(18)F]fluoroestradiol (4FMFES) by PET imaging in a breast cancer murine model.
abstract: OBJECTIVE
  The aim of this study was to compare the in vivo stability, uptake, and positron emission tomography (PET) imaging performance of a novel estrogen receptor PET tracer, 4-fluoro-11β-methoxy-16α-[(18)F]fluoroestradiol (4FMFES), with 16α-[(18)F]fluoroestradiol (FES).
  
  
  METHODS
  MC7-L1 and MC4-L2 (ER+) cell lines and their ERα-knockdown variants (ERαKD) were implanted subcutaneously in Balb/c mice. After 21 days, mice were imaged using either FES or 4FMFES. One hour post-injection, static images were acquired for 30 min and the tumor %ID/g uptake values were derived. Biodistribution data were also obtained 1 h following the injection of either FES or 4FMFES. Blood samples were taken at different times and analyzed on thin-layer chromatography to quantify the presence of radiometabolites for each radiotracer. To assess specific targeting to the estrogen receptors, mice bearing only ER+ tumors were treated with the competitive ER inhibitor fulvestrant 48 h prior to imaging with 4FMFES.
  
  
  RESULTS
  Metabolic stability was found to be similar for both tracers in mice. Both FES and 4FMFES differentiated ER+ tumors from ERαKD tumors in biodistribution and PET imaging studies. 4FMFES achieved a significantly higher %ID/g uptake in ER+ tumors and MC4-L2 ERαKD tumors than FES in the PET imaging studies. Also, tumor-to-background ratio was higher in ER+ tumors using 4FMFES compared to FES. Dissection data showed a significantly higher %ID/g in all tested cell lines and ER-rich tissues using 4FMFES versus FES. Fulvestrant-treated mice had either low or undetectable tumor uptake.
  
  
  CONCLUSIONS
  In a tumor-bearing mouse model, 4FMFES achieves better specific tumor uptake and better contrast than FES, making it a promising candidate for ER imaging.
authors.affiliation: Département de médecine nucléaire et radiobiologie, Sherbrooke Molecular Imaging Center, 3001, 12th Avenue, Sherbrooke, QC, J1H 5N4, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Paquette
authors.forename: Serge
authors.initials: S
authors.lastname: Phoenix
authors.forename: René
authors.initials: R
authors.lastname: Ouellet
authors.forename: Réjean
authors.initials: R
authors.lastname: Langlois
authors.forename: Johan E
authors.initials: JE
authors.lastname: van Lier
authors.forename: Eric E
authors.initials: EE
authors.lastname: Turcotte
authors.forename: Francois
authors.initials: F
authors.lastname: Bénard
authors.forename: Roger
authors.initials: R
authors.lastname: Lecomte
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media; D004195:Disease Models, Animal; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000000981:diagnostic imaging* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D049268:Positron-Emission Tomography; D011960:Receptors, Estrogen / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C521829:11-methoxy-4,16-difluoroestradiol; D003287:Contrast Media; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol; C043436:16-fluoroestradiol