title: Fluoroestradiol positron emission tomography reveals differences in pharmacodynamics of aromatase inhibitors, tamoxifen, and fulvestrant in patients with metastatic breast cancer.
abstract: OBJECTIVE
  To determine, by molecular imaging, how in vivo pharmacodynamics of estrogen-estrogen receptor (ER) binding differ between types of standard endocrine therapy.
  
  
  METHODS
  The ER has been a highly successful target for breast cancer treatment. ER-directed treatments include lowering ligand concentration by using aromatase inhibitors (AI) and blocking the receptor with agents like tamoxifen (TAM) or fulvestrant (FUL). We measured regional estrogen-ER binding by using positron emission tomography with (18)F-fluoroestradiol (FES PET) prior to and during treatment with AI, TAM, or FUL in a series of 30 metastatic breast cancer patients. FES PET measured in vivo estrogen binding at all tumor sites in heavily pretreated women with metastatic bone soft tissue-dominant breast cancer. In patients with uterus (n = 16) changes in uterine FES uptake were also measured.
  
  
  RESULTS
  As expected, tumor FES uptake declined more markedly on ER blockers (TAM and FUL, average 54% decline) compared with a less than 15% average decline on estrogen-depleting AIs (P < 0.001). The rate of complete tumor blockade [FES standardized uptake value (SUV) ≤1.5] following TAM (5/5 patients) was greater than the blockade rate following FUL (4/11; 2-sided mid P = 0.019). Percent FES SUV change in the uterus showed a strong association with tumoral change (ρ = 0.63, P = 0.01).
  
  
  CONCLUSIONS
  FES PET can assess the in vivo pharmacodynamics of ER-targeted agents and may give insight into the activity of established therapeutic agents. Imaging revealed significant differences between agents, including differences in the efficacy of blockade by different ER antagonists in current clinical use.
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, USA. hmlinden@u.washington.edu
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Linden
authors.forename: Brenda F
authors.initials: BF
authors.lastname: Kurland
authors.forename: Lanell M
authors.initials: LM
authors.lastname: Peterson
authors.forename: Erin K
authors.initials: EK
authors.lastname: Schubert
authors.forename: Julie R
authors.initials: JR
authors.lastname: Gralow
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Specht
authors.forename: Georgiana K
authors.initials: GK
authors.lastname: Ellis
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Lawton
authors.forename: Robert B
authors.initials: RB
authors.lastname: Livingston
authors.forename: Philip H
authors.initials: PH
authors.lastname: Petra
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Link
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Krohn
authors.forename: David A
authors.initials: DA
authors.lastname: Mankoff
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D049268:Positron-Emission Tomography; D012189:Retrospective Studies; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D013629:Tamoxifen / Q000627:therapeutic use*; D014599:Uterus / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol; C043436:16-fluoroestradiol