title: Utility of18F-fluoroestradiol (18F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy.
abstract: BACKGROUND
  Z-endoxifen is the most potent of the metabolites of tamoxifen, and has the potential to be more effective than tamoxifen because it bypasses potential drug resistance mechanisms attributable to patient variability in the expression of the hepatic microsomal enzyme CYP2D6.18F-FES is a positron emission tomography (PET) imaging agent which selectively binds to estrogen receptor alpha (ER-α) and has been used for non-invasive in vivo assessment of ER activity in tumors. This study utilizes18F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen.
  
  
  METHODS
  Fifteen patients were recruited from a parent therapeutic trial of Z-endoxifen and underwent imaging with18F-FES PET at baseline. Eight had positive lesions on the baseline scan and underwent follow-up imaging with18F-FES 1-5 days post administration of Z-endoxifen.
  
  
  RESULTS
  Statistically significant changes (p = 0.0078) in standard uptake value (SUV)-Max were observed between the baseline and follow-up scans as early as 1 day post drug administration.
  
  
  CONCLUSIONS
  F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy.
authors.affiliation: Cancer Imaging Program, National Cancer Institute, NIH, Bethesda, MD, USA. frank.lin2@nih.gov.|Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA. frank.lin2@nih.gov.
authors.forename: Frank I
authors.initials: FI
authors.lastname: Lin
authors.affiliation: Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Gonzalez
authors.affiliation: Division of Cancer Treatment and Diagnosis and Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kummar
authors.affiliation: Division of Cancer Treatment and Diagnosis and Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: K
authors.initials: K
authors.lastname: Do
authors.affiliation: Biometric Research Program, National Cancer Institute, NIH, Bethesda, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Shih
authors.affiliation: Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., NCI Campus at Frederick, Frederick, MD, 21702, USA.
authors.forename: S
authors.initials: S
authors.lastname: Adler
authors.affiliation: Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Kurdziel
authors.affiliation: Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ton
authors.affiliation: Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA.
authors.forename: B
authors.initials: B
authors.lastname: Turkbey
authors.affiliation: Cancer Imaging Program, National Cancer Institute, NIH, Bethesda, MD, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Jacobs
authors.affiliation: Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Frederick, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Bhattacharyya
authors.affiliation: Early Clinical Trials Development Program, DCTD, National Cancer Institute, Bethesda, MD, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Chen
authors.affiliation: Division of Cancer Treatment and Diagnosis and Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Collins
authors.affiliation: Division of Cancer Treatment and Diagnosis and Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Doroshow
authors.affiliation: Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA.
authors.forename: P L
authors.initials: PL
authors.lastname: Choyke
authors.affiliation: Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Lindenberg
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000235:genetics; D018567:Breast Neoplasms, Male / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000235:genetics; D004958:Estradiol / Q000031:analogs & derivatives*; D004965:Estrogen Antagonists / Q000627:therapeutic use; D005260:Female; D005833:Genital Neoplasms, Female / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D000072078:Positron Emission Tomography Computed Tomography; D019275:Radiopharmaceuticals; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000235:genetics; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D004965:Estrogen Antagonists; D019275:Radiopharmaceuticals; D011960:Receptors, Estrogen; D013629:Tamoxifen; C055492:4-hydroxy-N-desmethyltamoxifen; D004958:Estradiol; C043436:16-fluoroestradiol
keywords: 18F-FES; Fluoroestradiol; Pharmacodynamic marker; Positron emission tomography (PET); Z-endoxifen