title: PET imaging of neuroinflammation in a rat traumatic brain injury model with radiolabeled TSPO ligand DPA-714.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Xuyi
authors.initials: X
authors.lastname: Yue
authors.forename: Dale O
authors.initials: DO
authors.lastname: Kiesewetter
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.forename: Gaojun
authors.initials: G
authors.lastname: Teng
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D001930:Brain Injuries / Q000000981:diagnostic imaging* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18; D005786:Gene Expression Regulation; D007249:Inflammation / Q000000981:diagnostic imaging / Q000378:metabolism; D008024:Ligands; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D011720:Pyrazoles / Q000378:metabolism*; D011743:Pyrimidines / Q000378:metabolism*; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D008024:Ligands; C530129:N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D011963:Receptors, GABA-A; D019788:Fluorodeoxyglucose F18; C069997:Tspo protein, rat