title: Monitoring the effect of targeted therapies in a gastrointestinal stromal tumor xenograft using a clinical PET/CT.
abstract: OBJECTIVE
  The purpose of this study is to assess treatment responses induced by the two tyrosine kinase inhibitors, Imatinib and Sunitinib, in a gastrointestinal stromal tumor (GIST) xenograft using a clinical positron emission tomography/computed tomography (PET/CT) scanner.
  
  
  METHODS
  Nude mice bearing human GIST xenografts with mutations in exons 11 and 17 were randomly allocated to treatment with Imatinib, Sunitinib, or placebo daily for seven consecutive days. 2-deoxy-2-[(18)F]fluoro-D: -glucose PET ((18)F-FDG-PET/CT) was performed in a clinical PET/CT scanner at baseline (day 0) and 1 and 7 days after onset of treatment. Treatment response was assessed by measuring tumor volumes and by calculation of tumor-to-liver (18)F-FDG uptake ratios.
  
  
  RESULTS
  Minor reductions in tumor volume were observed in both treatment groups. For the two treatment groups, significantly decreased tumor-to-liver uptake ratios were observed both at day 1 (Imatinib, -41%, p = .002; Sunitinib, -55%, p < .001) and at day 8 (Imatinib, -35%, p < .001; Sunitinib, -50%, p < .001), when compared to individual baseline values. For the control tumors, neither tumor volumes nor tumor-to-liver uptake ratios were altered during the 8 days the experiment lasted.
  
  
  CONCLUSIONS
  Significant anti-tumor effects were demonstrated following treatment with both Imatinib and Sunitinib. Decreased tumor-to-liver uptake ratios were more pronounced than tumor volume reductions. Effects of novel targeted therapies can be evaluated in the GIST xenograft model using a clinical PET/CT scanner.
authors.affiliation: Department of Nuclear Medicine, Oslo University Hospital, Oslo, Norway. mona.elisabeth.revheim@ous-hf.no
authors.forename: Mona-Elisabeth
authors.initials: ME
authors.lastname: Revheim
authors.forename: Kathrine
authors.initials: K
authors.lastname: Røe
authors.forename: Øyvind Sverre
authors.initials: ØS
authors.lastname: Bruland
authors.forename: Tore
authors.initials: T
authors.lastname: Bach-Gansmo
authors.forename: Arne
authors.initials: A
authors.lastname: Skretting
authors.forename: Therese
authors.initials: T
authors.lastname: Seierstad
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D016903:Drug Monitoring; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use; D000077210:Sunitinib; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib