Establishment of a mouse gastrointestinal stromal tumour model and evaluation of response to imatinib by small animal positron emission tomography.
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.
Prenen
Hans
H
Laboratory for Experimental Oncology (LEO), Department of General Medical Oncology, Catholic University Leuven, B-3000 Leuven, Belgium. hans.prenen@uz.kuleuven.ac.be
Deroose
Christophe
C
Vermaelen
Peter
P
Sciot
Raf
R
Debiec-Rychter
Maria
M
Stroobants
Sigrid
S
Mortelmans
Luc
L
Schöffski
Patrick
P
Van Oosterom
Allan
A
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
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D019788:Fluorodeoxyglucose F18; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit