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.
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 SDrats 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.
Authors: Matthias Schilling; Michael Besselmann; Marcus Müller; Jan K Strecker; E Bernd Ringelstein; Reinhard Kiefer Journal: Exp Neurol Date: 2005-09-08 Impact factor: 5.330
Authors: Dimitrios Davalos; Jaime Grutzendler; Guang Yang; Jiyun V Kim; Yi Zuo; Steffen Jung; Dan R Littman; Michael L Dustin; Wen-Biao Gan Journal: Nat Neurosci Date: 2005-05-15 Impact factor: 24.884
Authors: Hervé Boutin; Christian Prenant; Renaud Maroy; James Galea; Andrew D Greenhalgh; Alison Smigova; Christopher Cawthorne; Peter Julyan; Shane M Wilkinson; Samuel D Banister; Gavin Brown; Karl Herholz; Michael Kassiou; Nancy J Rothwell Journal: PLoS One Date: 2013-02-13 Impact factor: 3.240
Authors: Arthur L Brody; Robert Hubert; Ryutaro Enoki; Lizette Y Garcia; Michael S Mamoun; Kyoji Okita; Edythe D London; Erika L Nurmi; Lauren C Seaman; Mark A Mandelkern Journal: Neuropsychopharmacology Date: 2017-03-06 Impact factor: 7.853
Authors: Cornelius K Donat; Khaled Gaber; Jürgen Meixensberger; Peter Brust; Lars H Pinborg; Henrik H Hansen; Jens D Mikkelsen Journal: Neuromolecular Med Date: 2016-03-11 Impact factor: 3.843
Authors: Rahul M Nikam; Xuyi Yue; Vinay V Kandula; Bishnuhari Paudyal; Sigrid A Langhans; Lauren W Averill; Arabinda K Choudhary Journal: Pediatr Radiol Date: 2021-05-17
Authors: Bin Liu; Kevin X Le; Mi-Ae Park; Shuyan Wang; Anthony P Belanger; Shipra Dubey; Jeffrey L Frost; Peter Holton; Vladimir Reiser; Paul A Jones; William Trigg; Marcelo F Di Carli; Cynthia A Lemere Journal: J Neurosci Date: 2015-11-25 Impact factor: 6.167