title: Establishment of a mouse gastrointestinal stromal tumour model and evaluation of response to imatinib by small animal positron emission tomography.
abstract: BACKGROUND
  Gastrointestinal stromal tumours (GIST) predominantly express activating mutations of the KIT tyrosine kinase receptor and are successfully treated with imatinib mesylate, a KIT inhibitor. As resistance to imatinib causes therapy failure, our aim was to develop an in vivo GIST model to evaluate KIT inhibitors and monitor therapy with small animal positron emission tomography (PET).
  
  
  METHODS
  The first mouse model of GIST xenografts was successfully established by injecting GIST882 cells subcutaneously into nude mice.
  
  
  RESULTS
  Using the small animal PET, FDG up-take in xenografts was significantly decreased after 24 h of treatment with imatinib, which correlated with a response to treatment, e.g., with a decrease in tumour volume, the inhibition of KIT and downstream intermediate phosphorylation and arrest of tumour cell proliferation as evaluated after 7 days of treatment.
  
  
  CONCLUSIONS
  This model is useful to study imatinib resistance and to evaluate novel targeted therapies.
authors.affiliation: Laboratory for Experimental Oncology (LEO), Department of General Medical Oncology, Catholic University Leuven, B-3000 Leuven, Belgium. hans.prenen@uz.kuleuven.ac.be
authors.forename: Hans
authors.initials: H
authors.lastname: Prenen
authors.forename: Christophe
authors.initials: C
authors.lastname: Deroose
authors.forename: Peter
authors.initials: P
authors.lastname: Vermaelen
authors.forename: Raf
authors.initials: R
authors.lastname: Sciot
authors.forename: Maria
authors.initials: M
authors.lastname: Debiec-Rychter
authors.forename: Sigrid
authors.initials: S
authors.lastname: Stroobants
authors.forename: Luc
authors.initials: L
authors.lastname: Mortelmans
authors.forename: Patrick
authors.initials: P
authors.lastname: Schöffski
authors.forename: Allan
authors.initials: A
authors.lastname: Van Oosterom
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D015153:Blotting, Western; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D046152:Gastrointestinal Stromal Tumors / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D010879:Piperazines / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D019788:Fluorodeoxyglucose F18; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit