Monitoring the effect of targeted therapies in a gastrointestinal stromal tumor xenograft using a clinical PET/CT.

摘要

PURPOSE: 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.