title: FDG-PET for pharmacodynamic assessment of the fatty acid synthase inhibitor C75 in an experimental model of lung cancer.
abstract: OBJECTIVE
  Fatty acid synthase (FAS) is an emerging target for anticancer therapy with a variety of new FAS inhibitors being explored in preclinical models. The aim of this study was to use positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) to monitor the effects of the FAS inhibitor C75 on tumor glucose metabolism in a rodent model of human A549 lung cancer.
  
  
  METHODS
  After a baseline FDG-PET scan, C75 was administered and post-treatment scans were performed serially. FAS activity was measured in treated animals ex vivo by [(14)C]acetate incorporation in animals euthanized in parallel to those imaged.
  
  
  RESULTS
  Longitudinally measured metabolic volumes of interest and tumor/background ratios demonstrated a transient, reversible decrease in glucose metabolism and tumor metabolic volume after treatment, with the peak effect seen at 4 h. FDG-PET measurements correlated with changes in tumor FAS activity measured ex vivo.
  
  
  CONCLUSIONS
  Because C75 causes an effect that is shorter in duration than expected, modification of the current weekly dosing regimen should be considered. These results demonstrate the utility of small animal FDG-PET in assessing the pharmacodynamics of new anticancer agents in preclinical models.
authors.affiliation: Department of Radiology, Johns Hopkins Medical Institutions, 1550 Orleans Street, 492 CRB II, Baltimore, Maryland 21231, USA.
authors.forename: Jae Sung
authors.initials: JS
authors.lastname: Lee
authors.forename: Hajime
authors.initials: H
authors.lastname: Orita
authors.forename: Kathleen
authors.initials: K
authors.lastname: Gabrielson
authors.forename: Sara
authors.initials: S
authors.lastname: Alvey
authors.forename: Ruth L
authors.initials: RL
authors.lastname: Hagemann
authors.forename: Francis P
authors.initials: FP
authors.lastname: Kuhajda
authors.forename: Edward
authors.initials: E
authors.lastname: Gabrielson
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors*; D019788:Fluorodeoxyglucose F18; D008175:Lung Neoplasms / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D051381:Rats
chemical_list: C406734:4-methylene-2-octyl-5-oxofuran-3-carboxylic acid; D004791:Enzyme Inhibitors; D019788:Fluorodeoxyglucose F18; D064429:Fatty Acid Synthases; D015107:4-Butyrolactone