title: PET imaging of TSPO in a rat model of local neuroinflammation induced by intracerebral injection of lipopolysaccharide.
abstract: OBJECTIVE
  The goal of this study was to measure functional and structural aspects of local neuroinflammation induced by intracerebral injection of lipopolysaccharide (LPS) in rats using TSPO microPET imaging with [(18)F]DPA-714, magnetic resonance imaging (MRI), in vitro autoradiography and immunohistochemistry (IHC) in order to characterize a small animal model for screening of new PET tracers targeting neuroinflammation.
  
  
  METHODS
  Rats were injected stereotactically with LPS (50 μg) in the right striatum and with saline in the left striatum. [(18)F]DPA-714 microPET, MRI, in vitro autoradiography and IHC studies were performed at different time points after LPS injection for 1 month.
  
  
  RESULTS
  Analysis of the microPET data demonstrated high uptake of the tracer in the LPS injected site with an affected-to-non-affected side-binding potential ratio (BPright-to-left) of 3.0 at 3 days after LPS injection. This BP ratio decreased gradually over time to 0.9 at 30 days after LPS injection. In vitro autoradiography ([(18)F]DPA-714) and IHC (CD68, GFAP and TSPO) confirmed local neuroinflammation in this model. Dynamic contrast enhanced (DCE) MRI demonstrated BBB breakdown near the LPS injection site at day 1, which gradually resolved over time and was absent at 1 month after LPS injection.
  
  
  CONCLUSIONS
  The LPS model is useful for first screening of newly developed tracers because of the easy design and the robust, unilateral inflammatory reaction allowing the use of the contralateral region as control. Additionally, this model can be used to test and follow up the benefits of anti-inflammatory therapies by non-invasive imaging.
authors.affiliation: Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Dieter
authors.initials: D
authors.lastname: Ory
authors.affiliation: Department of Brain Ischemia and Neurodegeneration, Institute for Biomedical Research, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Planas
authors.affiliation: Biomedical MRI, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Dresselaers
authors.affiliation: Biomedical MRI, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Willy
authors.initials: W
authors.lastname: Gsell
authors.affiliation: Nuclear Medicine and Molecular Imaging, University Hospital and KU Leuven, Leuven, Belgium.
authors.forename: Andrey
authors.initials: A
authors.lastname: Postnov
authors.affiliation: Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Celen
authors.affiliation: Nuclear Medicine and Molecular Imaging, University Hospital and KU Leuven, Leuven, Belgium.
authors.forename: Cindy
authors.initials: C
authors.lastname: Casteels
authors.affiliation: Biomedical MRI, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Uwe
authors.initials: U
authors.lastname: Himmelreich
authors.affiliation: Laboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.affiliation: Nuclear Medicine and Molecular Imaging, University Hospital and KU Leuven, Leuven, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Van Laere
authors.affiliation: Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Alfons
authors.initials: A
authors.lastname: Verbruggen
authors.affiliation: Laboratory for Radiopharmacy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium. Electronic address: Guy.Bormans@pharm.kuleuven.be.
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005462:Fluorine Radioisotopes; D007249:Inflammation / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism; D007267:Injections; D008070:Lipopolysaccharides / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D011720:Pyrazoles; D011743:Pyrimidines; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D005462:Fluorine Radioisotopes; D008070:Lipopolysaccharides; 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; C069997:Tspo protein, rat
keywords: Lipopolysaccharide; Neuroinflammation; PET; [(18)F]DPA-714