Buck Jason R, McKinley Eliot T, Fu Allie, Abel Ty W, Thompson Reid C, Chambless Lola, Watchmaker Jennifer M, Harty James P, Cooper Michael K, Manning H Charles
Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center, Nashville, TN, United States of America.
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America.
PLoS One. 2015 Oct 30;10(10):e0141659. doi: 10.1371/journal.pone.0141659. eCollection 2015.
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.
目前用于检测浸润性胶质瘤的正电子发射断层扫描（PET）成像生物标志物有限。转运蛋白（TSPO）是一种用于胶质瘤PET成像的新型且有前景的生物标志物。为了验证TSPO作为胶质瘤分子成像的潜在靶点，在包含37例高级别（III、IV级）胶质瘤的肿瘤微阵列中检测了TSPO的表达。在所有肿瘤标本中均检测到TSPO染色。随后，在WHO III级和IV级胶质瘤的原发性原位异种移植模型中，使用基于芳氧基苯胺的TSPO配体[18F]PBR06进行PET成像。测量了[18F]PBR06在移植瘤中的选择性摄取。此外，用[18F]PBR06进行的PET成像显示出传统磁共振成像（MRI）无法检测到的浸润性胶质瘤生长。与2-脱氧-2-[18F]氟-D-葡萄糖（[18F]FDG）相比，用[18F]PBR06进行的初步PET显示出肿瘤与正常背景的优先比值。这些结果表明，使用这种高亲和力放射性示踪剂进行TSPO PET成像可能代表一种新的策略，用于表征胶质瘤生长的独特分子特征，以及更好地确定用于治疗目的的胶质瘤浸润范围。
