PET imaging of TSPO in a rat model of local neuroinflammation induced by intracerebral injection of lipopolysaccharide

Abstract

ObjectiveThe 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 [18F]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. MethodsRats were injected stereotactically with LPS (50μg) in the right striatum and with saline in the left striatum. [18F]DPA-714 microPET, MRI, in vitro autoradiography and IHC studies were performed at different time points after LPS injection for 1month. ResultsAnalysis 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 3days after LPS injection. This BP ratio decreased gradually over time to 0.9 at 30days after LPS injection. In vitro autoradiography ([18F]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 1month after LPS injection. ConclusionThe 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.