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

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 immunohistochemistly (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 mu g) 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 aft 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. Conclusion: 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. (C) 2015 Elsevier Inc. All rights reserved.