title: Longitudinal noninvasive imaging of progesterone receptor as a predictive biomarker of tumor responsiveness to estrogen deprivation therapy.
abstract: OBJECTIVE
  To investigate whether longitudinal functional PET imaging of mammary tumors using the radiopharmaceuticals [(18)F]FDG (to measure glucose uptake), [(18)F]FES [to measure estrogen receptor (ER) levels], or [(18)F]FFNP [to measure progesterone receptor (PgR) levels] is predictive of response to estrogen-deprivation therapy.
  
  
  METHODS
  [(18)F]FDG, [(18)F]FES, and [(18)F]FFNP uptake in endocrine-sensitive and -resistant mammary tumors was quantified serially by PET before ovariectomy or estrogen withdrawal in mice, and on days 3 and 4 after estrogen-deprivation therapy. Specificity of [(18)F]FFNP uptake in ERα(+) mammary tumors was determined by competition assay using unlabeled ligands for PgR or glucocorticoid receptor (GR). PgR expression was also assayed by immunohistochemistry (IHC).
  
  
  RESULTS
  The levels of [(18)F]FES and [(18)F]FDG tumor uptake remained unchanged in endocrine-sensitive tumors after estrogen-deprivation therapy compared with those at pretreatment. In contrast, estrogen-deprivation therapy led to a reduction in PgR expression and [(18)F]FFNP uptake in endocrine-sensitive tumors, but not in endocrine-resistant tumors, as early as 3 days after treatment; the changes in PgR levels were confirmed by IHC. Unlabeled PgR ligand R5020 but not GR ligand dexamethasone blocked [(18)F]FFNP tumor uptake, indicating that [(18)F]FFNP bound specifically to PgR. Therefore, a reduction in FFNP tumor to muscle ratio in mammary tumors predicts sensitivity to estrogen-deprivation therapy.
  
  
  CONCLUSIONS
  Monitoring the acute changes in ERα activity by measuring [(18)F]FFNP uptake in mammary tumors predicts tumor response to estrogen-deprivation therapy. Longitudinal noninvasive PET imaging using [(18)F]FFNP is a robust and effective approach to predict tumor responsiveness to endocrine treatment.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri. schan@pathology.wustl.edu jkatzene@illinois.edu.
authors.forename: Szeman Ruby
authors.initials: SR
authors.lastname: Chan
authors.affiliation: Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Fowler
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Allen
authors.affiliation: Division of Radiological Sciences, Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Division of Radiological Sciences, Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Carmen S
authors.initials: CS
authors.lastname: Dence
authors.affiliation: Division of Radiological Sciences, Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Terry L
authors.initials: TL
authors.lastname: Sharp
authors.affiliation: Division of Radiological Sciences, Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Fettig
authors.affiliation: Division of Radiological Sciences, Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Farrokh
authors.initials: F
authors.lastname: Dehdashti
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois. schan@pathology.wustl.edu jkatzene@illinois.edu.
authors.forename: John A
authors.initials: JA
authors.lastname: Katzenellenbogen
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000494:pharmacology; D015415:Biomarkers; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm; D047628:Estrogen Receptor alpha; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008024:Ligands; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D049268:Positron-Emission Tomography; D011397:Promegestone / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000378:metabolism*; D014057:Tomography, X-Ray Computed
chemical_list: D018931:Antineoplastic Agents, Hormonal; D015415:Biomarkers; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D008024:Ligands; D011980:Receptors, Progesterone; D019788:Fluorodeoxyglucose F18; D011397:Promegestone