title: [18F]FDG and [18F]FLT positron emission tomography imaging following treatment with belinostat in human ovary cancer xenografts in mice.
abstract: BACKGROUND
  Belinostat is a histone deacetylase inhibitor with anti-tumor effect in several pre-clinical tumor models and clinical trials. The aim of the study was to evaluate changes in cell proliferation and glucose uptake by use of 3'-deoxy-3'-[(18)F]fluorothymidine ([18F]FLT) and 2-deoxy-2-[(18)F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) following treatment with belinostat in ovarian cancer in vivo models.
  
  
  METHODS
  In vivo uptake of [18F]FLT and [18F]FDG in human ovary cancer xenografts in mice (A2780) were studied after treatment with belinostat. Mice were divided in 2 groups receiving either belinostat (40 mg/kg ip twice daily Day 0-4 and 6-10) or vehicle. Baseline [18F]FLT or [18F]FDG scans were made before treatment (Day 0) and repeated at Day 3, 6 and 10. Tracer uptake was quantified using small animal PET/CT.
  
  
  RESULTS
  Tumors in the belinostat group had volumes that were 462 ± 62% (640 mm(3)) at Day 10 relative to baseline which was significantly different (P = 0.011) from the control group 769 ± 74% (926 mm(3)). [18F]FLT SUVmax increased from baseline to Day 10 (+30 ± 9%; P = 0.048) in the control group. No increase was observed in the treatment group. [18F]FDG SUVmean was significantly different in the treatment group compared to the control group (P = 0.0023) at Day 10. Within treatment groups [18F]FDG uptake and to a lesser extent [18F]FLT uptake at Day 3 were significantly correlated with tumor growth at Day 10.
  
  
  CONCLUSIONS
  [18F]FDG uptake early following treatment initiation predicted tumor sizes at Day 10, suggesting that [18F]FDG may be a valuable biomarker for non-invasive assessment of anti-tumor activity of belinostat.
authors.affiliation: Cluster for Molecular Imaging, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 12.3.11, Copenhagen N 2200, Denmark. mettemj@sund.ku.dk
authors.forename: Mette Munk
authors.initials: MM
authors.lastname: Jensen
authors.forename: Kamille Dumong
authors.initials: KD
authors.lastname: Erichsen
authors.forename: Camilla Bardram
authors.initials: CB
authors.lastname: Johnbeck
authors.forename: Fredrik
authors.initials: F
authors.lastname: Björkling
authors.forename: Jacob
authors.initials: J
authors.lastname: Madsen
authors.forename: Peter Buhl
authors.initials: PB
authors.lastname: Jensen
authors.forename: Maxwell
authors.initials: M
authors.lastname: Sehested
authors.forename: Liselotte
authors.initials: L
authors.lastname: Højgaard
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjær
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D015224:Dideoxynucleosides; D004195:Disease Models, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18; D051272:Glucose Transporter Type 1 / Q000235:genetics; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000627:therapeutic use; D019394:Ki-67 Antigen / Q000235:genetics; D051379:Mice; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use; D013937:Thymidine Kinase / Q000235:genetics; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D015224:Dideoxynucleosides; D051272:Glucose Transporter Type 1; D006877:Hydroxamic Acids; D019394:Ki-67 Antigen; D019275:Radiopharmaceuticals; D013449:Sulfonamides; D019788:Fluorodeoxyglucose F18; D013937:Thymidine Kinase; C092717:thymidine kinase 1; C487081:belinostat; C002854:alovudine
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