放射性标记 TSPO 配体 DPA-714 对大鼠创伤性脑损伤模型神经炎症的 PET 成像。
PET imaging of neuroinflammation in a rat traumatic brain injury model with radiolabeled TSPO ligand DPA-714.
机构信息
Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009, China.
出版信息
Eur J Nucl Med Mol Imaging. 2014 Jul;41(7):1440-9. doi: 10.1007/s00259-014-2727-5. Epub 2014 Mar 11.
PURPOSE
The inflammatory response in injured brain parenchyma after traumatic brain injury (TBI) is crucial in the pathological process. In order to follow microglia activation and neuroinflammation after TBI, we performed PET imaging in a rat model of TBI using (18)F-labeled DPA-714, a ligand of the 18-kDa translocator protein (TSPO).
METHODS
TBI was induced in male SD rats by a controlled cortical impact. The success of the TBI model was confirmed by MRI. [(18)F]DPA-714 was synthesized using a slightly modified TRACERLab FX-FN module and an automated procedure. In vivo PET imaging was performed at different time points after surgery using an Inveon small-animal PET scanner. The specificity of [(18)F]DPA-714 was confirmed by a displacement study with an unlabeled competitive TSPO ligand, PK11195. Ex vivo autoradiography as well as immunofluorescence staining was carried out to confirm the in vivo PET results.
RESULTS
Both in vivo T2-weighted MR images and ex vivo TTC staining results revealed successful establishment of the TBI model. Compared with the sham-treated group, [(18)F]DPA-714 uptake was significantly higher in the injured brain area on PET images. Increased lesion-to-normal ratios of [(18)F]DPA-714 were observed in the brain of TBI rats on day 2 after surgery. Ratios peaked around day 6 (2.65 ± 0.36) and then decreased gradually to nearly normal levels on day 28. The displacement study using PK11195 confirmed the specific binding of [(18)F]DPA-714 to TSPO. The results of ex vivo autoradiography were consistent with in vivo PET results. Immunofluorescence staining showed the time course of TSPO expression after TBI and the temporal and the spatial distribution of microglia in the damaged brain area.
CONCLUSION
TSPO-targeted PET using [(18)F]DPA-714 as the imaging probe can be used to dynamically monitor the inflammatory response after TBI in a noninvasive manner. This method will not only facilitate a better understanding of the inflammatory process after TBI, but also provide a useful in vivo monitoring strategy for antiinflammation therapy of TBI.
目的
创伤性脑损伤（TBI）后损伤脑组织中的炎症反应在病理过程中至关重要。为了跟踪 TBI 后小胶质细胞的激活和神经炎症，我们使用（18）F 标记的 DPA-714（TSPO 的 18kDa 转位蛋白配体）对 TBI 大鼠模型进行了 PET 成像。
方法
雄性 SD 大鼠通过皮质冲击控制诱导 TBI。通过 MRI 确认 TBI 模型的成功。使用经过轻微修改的 TRACERLab FX-FN 模块和自动化程序合成[（18）F]DPA-714。使用 Inveon 小动物 PET 扫描仪在手术后的不同时间点进行体内 PET 成像。通过使用未标记的竞争性 TSPO 配体 PK11195 进行置换研究，证实了[（18）F]DPA-714 的特异性。进行离体放射性自显影和免疫荧光染色以证实体内 PET 结果。
结果
体内 T2 加权磁共振图像和离体 TTC 染色结果均显示 TBI 模型的成功建立。与假手术处理组相比，PET 图像显示受伤脑区的[（18）F]DPA-714 摄取明显升高。手术后第 2 天，TBI 大鼠的脑损伤区观察到[（18）F]DPA-714 的病变与正常比值增加。比值在术后第 6 天左右达到峰值（2.65±0.36），然后逐渐降至第 28 天接近正常水平。使用 PK11195 进行的置换研究证实了[（18）F]DPA-714 与 TSPO 的特异性结合。离体放射性自显影的结果与体内 PET 结果一致。免疫荧光染色显示了 TBI 后 TSPO 表达的时间过程以及损伤脑区小胶质细胞的时空分布。
结论
使用[（18）F]DPA-714 作为成像探针的 TSPO 靶向 PET 可用于非侵入性地动态监测 TBI 后的炎症反应。这种方法不仅将有助于更好地了解 TBI 后的炎症过程，还将为 TBI 的抗炎治疗提供有用的体内监测策略。
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