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Preclinical TSPO Ligand PET to Visualize Human Glioma Xenotransplants: A Preliminary Study
Authors:Jason R Buck  Eliot T McKinley  Allie Fu  Ty W Abel  Reid C Thompson  Lola Chambless  Jennifer M Watchmaker  James P Harty  Michael K Cooper  H Charles Manning
Abstract:Current positron emission tomography (PET) imaging biomarkers for detection of infiltrating gliomas are limited. Translocator protein (TSPO) is a novel and promising biomarker for glioma PET imaging. To validate TSPO as a potential target for molecular imaging of glioma, TSPO expression was assayed in a tumor microarray containing 37 high-grade (III, IV) gliomas. TSPO staining was detected in all tumor specimens. Subsequently, PET imaging was performed with an aryloxyanilide-based TSPO ligand, 18F]PBR06, in primary orthotopic xenograft models of WHO grade III and IV gliomas. Selective uptake of 18F]PBR06 in engrafted tumor was measured. Furthermore, PET imaging with 18F]PBR06 demonstrated infiltrative glioma growth that was undetectable by traditional magnetic resonance imaging (MRI). Preliminary PET with 18F]PBR06 demonstrated a preferential tumor-to-normal background ratio in comparison to 2-deoxy-2-18F]fluoro-D-glucose (18F]FDG). These results suggest that TSPO PET imaging with such high-affinity radiotracers may represent a novel strategy to characterize distinct molecular features of glioma growth, as well as better define the extent of glioma infiltration for therapeutic purposes.
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