title: [(18)F]DPA-714 PET imaging of AMD3100 treatment in a mouse model of stroke.
abstract: Chemokine receptor 4 and stromal-cell-derived factor 1 have been found to be related to the initiation of neuroinflammation in ischemic brain. Herein, we aimed to monitor the changes of neuorinflammation after AMD3100 treatment using a translocator protein (TSPO) specific PET tracer in a mouse model of stroke. The transient MCAO model was established with Balb/C mice. The success of the model was confirmed by magnetic resonance imaging and FDG PET. The treatment started the same day after surgery via daily intraperitoneal injection of 1 mg of AMD3100/kg for three consecutive days. [(18)F]DPA-714 was used as the TSPO imaging tracer. In vivo PET was performed at different time points after surgery in both control and treated mice. Ex vivo histological and immunofluorescence staining of brain slices was performed to confirm the lesion site and inflammatory cell activation. The TSPO level was also evaluated using Western blotting. Longitudinal PET scans revealed that the level of [(18)F]DPA-714 uptake was significantly increased in the ischemic brain area with a peak accumulation at around day 10 after surgery, and the level of uptake remained high until day 16. The in vivo PET data were consistent with those from ex vivo immunofluorescence staining. After AMD3100 treatment, the signal intensity was significantly decreased compared with that of normal saline-treated control group. In conclusion, TSPO-targeted PET imaging using [(18)F]DPA-714 can be used to monitor inflammatory response after stroke and provide a useful method for evaluating the efficacy of anti-inflammation treatment.
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: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
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; D001596:Benzylamines; D000080027:Cyclams; D004195:Disease Models, Animal; D005462:Fluorine Radioisotopes; D006571:Heterocyclic Compounds / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D049268:Positron-Emission Tomography / Q000379:methods*; D011720:Pyrazoles; D011743:Pyrimidines; D020521:Stroke / Q000175:diagnosis* / Q000188:drug therapy*
chemical_list: D001596:Benzylamines; D000080027:Cyclams; D005462:Fluorine Radioisotopes; D006571:Heterocyclic Compounds; C530129:N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide; D011720:Pyrazoles; D011743:Pyrimidines; C088327:plerixafor
keywords: AMD3100; DPA-714; PET; stroke; translocator protein (TSPO)