title: Comparison of (18)F-FET and (18)F-FLT small animal PET for the assessment of anti-VEGF treatment response in an orthotopic model of glioblastoma.
abstract: BACKGROUND
  The radiolabeled amino acid O-(2-(18)F-fluoroethyl)-L-tyrosine (FET) and thymidine analogue 3'-deoxy-3'-(18)F-fluorothymidine (FLT) are widely used for positron emission tomography (PET) brain tumor imaging; however, comparative studies are scarce. The aim of this study therefore was to compare FLT and FET PET for the assessment of anti-VEGF response in glioblastoma xenografts.
  
  
  METHODS
  Xenografts with confirmed intracranial glioblastoma were treated with anti-VEGF therapy (B20-4.1) or saline as control. Weekly bioluminescence imaging (BLI), FLT and FET PET/CT were used to follow treatment response. Tracer uptake of FLT and FET was quantified using maximum standardized uptake (SUVmax) values and tumor-to-background ratios (TBRs). Survival, the Ki67 proliferation index and micro-vessel density (MVD) were evaluated.
  
  
  RESULTS
  In contrast to FLT TBRs, FET TBRs were significantly lower as early as one week after treatment initiation in the anti-VEGF group as compared to the control group. Following two weeks of treatment, both FLT and FET TBRs were significantly lower in the anti-VEGF group. In contrast, no significant difference between the treatment groups was detected using BLI. Furthermore, we found a significantly lower MVD in the anti-VEGF group as compared to the control group. However, we found no difference in the Ki67 proliferation index or mean survival time.
  
  
  CONCLUSIONS
  FET appears to be a more sensitive tracer than FLT to measure early response to anti-VEGF therapy with PET. Advances in knowledge and implications for patient care FET PET appears to be an early predictor of anti-VEGF efficacy. Confirmation of these results in clinical studies is needed.
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark. Electronic address: Mette.kjoelhede.nedergaard@regionh.dk.
authors.forename: Mette Kjoelhede
authors.initials: MK
authors.lastname: Nedergaard
authors.affiliation: Department of Radiation Biology, The Finsen Center, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Signe Regner
authors.initials: SR
authors.lastname: Michaelsen
authors.affiliation: Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lara
authors.initials: L
authors.lastname: Perryman
authors.affiliation: Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark.
authors.forename: Janine
authors.initials: J
authors.lastname: Erler
authors.affiliation: Department of Radiation Biology, The Finsen Center, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Hans Skovgaard
authors.initials: HS
authors.lastname: Poulsen
authors.affiliation: Department of Radiation Biology, The Finsen Center, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Marie-Thérése
authors.initials: MT
authors.lastname: Stockhausen
authors.affiliation: Phase 1 Unit, Department of Oncology, The Finsen Center, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Lassen
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjaer
mesh_terms: D000818:Animals; D000068258:Bevacizumab / Q000276:immunology / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy; D002471:Cell Transformation, Neoplastic; D015224:Dideoxynucleosides; D005260:Female; D005909:Glioblastoma / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D055806:Microvessels / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D016019:Survival Analysis; D014443:Tyrosine / Q000031:analogs & derivatives*; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology*
chemical_list: D015224:Dideoxynucleosides; D042461:Vascular Endothelial Growth Factor A; C545932:(18F)fluoroethyltyrosine; D000068258:Bevacizumab; D014443:Tyrosine; C002854:alovudine
keywords: FET; FLT; Glioblastoma; Glioma; PET; Response