title: Downregulation of 18F-FDG uptake in PET as an early pharmacodynamic effect in treatment of non-small cell lung cancer with the mTOR inhibitor everolimus.
abstract: Everolimus downregulates glucose metabolism-associated genes in preclinical models. Inhibition of glucose metabolism measured by (18)F-FDG PET was postulated to serve as a pharmacodynamic marker in everolimus-treated non-small cell lung cancer (NSCLC) patients.
  
  
  METHODS
  In 8 NSCLC patients treated with everolimus, the percentage change in (18)F-FDG PET uptake (days 8 and 28 relative to baseline) was determined using a variety of summed standardized uptake value (SUV) measures. Both maximum and mean SUVs were used, with normalizations to body surface area and body weight and with and without correcting for plasma glucose levels.
  
  
  RESULTS
  In 5 patients, a reduction of (18)F-FDG PET uptake on day 8 was observed with all methods, ranging from -12.8% to -72.2%.
  
  
  CONCLUSIONS
  These observations demonstrate that inhibition of glucose metabolism is an early effect of everolimus treatment in NSCLC patients and can be assessed using (18)F-FDG PET.
authors.affiliation: Lung Cancer Group Cologne, Department I of Internal Medicine, Center for Integrated Oncology, University Hospital Cologne, Cologne, Germany.
authors.forename: Lucia
authors.initials: L
authors.lastname: Nogová
authors.forename: Ronald
authors.initials: R
authors.lastname: Boellaard
authors.forename: Carsten
authors.initials: C
authors.lastname: Kobe
authors.forename: Nikie
authors.initials: N
authors.lastname: Hoetjes
authors.forename: Thomas
authors.initials: T
authors.lastname: Zander
authors.forename: Stefan Hubert
authors.initials: SH
authors.lastname: Gross
authors.forename: Sasa
authors.initials: S
authors.lastname: Dimitrijevic
authors.forename: Theodore
authors.initials: T
authors.lastname: Pellas
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eschner
authors.forename: Katja
authors.initials: K
authors.lastname: Schmidt
authors.forename: Christopher
authors.initials: C
authors.lastname: Bangard
authors.forename: Wendy
authors.initials: W
authors.lastname: Hayes
authors.forename: Roman K
authors.initials: RK
authors.lastname: Thomas
authors.forename: Markus
authors.initials: M
authors.lastname: Dietlein
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giaccone
authors.forename: Otto S
authors.initials: OS
authors.lastname: Hoekstra
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wolf
mesh_terms: D000368:Aged; D001692:Biological Transport / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D000068338:Everolimus; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011494:Protein Kinases / Q000378:metabolism*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases; D013997:Time Factors
chemical_list: D047428:Protein Kinase Inhibitors; D019788:Fluorodeoxyglucose F18; D000068338:Everolimus; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D005947:Glucose; D020123:Sirolimus