科研之友
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摘要
The hypothesis of this study was that distinct experimental glioblastoma phenotypes resembling human disease can be noninvasively distinguished at various disease stages by imaging in vivo. Methods: Cultured spheroids from 2 human glioblastomas were implanted into the brains of nude rats. Glioblastoma growth dynamics were followed by PET using F-18-FDG, C-11-methyl-L-methionine (C-11-MET), and 3%26apos;-deoxy-3%26apos;-F-18-fluorothymidine (F-18-FLT) and by MRI at 3-6 wk after implantation. For image validation, parameters were coregistered with immunohistochemical analysis. Results: Two tumor phenotypes (angiogenic and infiltrative) were obtained. The angiogenic phenotype showed high uptake of C-11-MET and F-18-FLT and relatively low uptake of F-18-FDG. C-11-MET was an early indicator of vessel remodeling and tumor proliferation. F-18-FLT uptake correlated to positive Ki67 staining at 6 wk. T1- and T2-weighted MR images displayed clear tumor delineation with strong gadolinium enhancement at 6 wk. The infiltrative phenotype did not accumulate C-11-MET and F-18-FLT and impaired the F-18-FDG uptake. In contrast, the Ki67 index showed a high proliferation rate. The extent of the infiltrative tumors could be observed by MRI but with low contrast. Conclusion: For angiogenic glioblastomas, noninvasive assessment of tumor activity corresponds well to immunohistochemical markers, and C-11-MET was more sensitive than F-18-FLT at detecting early tumor development. In contrast, infiltrative glioblastoma growth in the absence of blood-brain barrier breakdown is difficult to noninvasively follow by existing imaging techniques, and a negative F-18-FLT PET result does not exclude the presence of proliferating glioma tissue. The angiogenic model may serve as an advanced system to study imaging-guided antiangiogenic and antiproliferative therapies.
- 出版日期2012-7
- 单位中国地震局
