Comparative Evaluation of Three TSPO PET Radiotracers in a LPS-Induced Model of Mild Neuroinflammation in Rats

• DOI: 10.1007/s11307-016-0984-3
• Publication Date: 2016-08-01T10:10:40Z
• Authors: Sujata Sridharan; Francois-Xavier L...; William Trigg; Samuel Banister; Tristan Reekie; Michael Kassiou; Alexander Gerhard; Rainer Hinz; Hervé Boutin
• Keywords: Rodent model; PET Imaging; Translocator protein

Over the past 20 years, neuroinflammation (NI) has increasingly been recognised as having an important role in many neurodegenerative diseases, including Alzheimer's disease. As such, being able to image NI non-invasively patients is critical monitor pathological processes and potential therapies targeting neuroinflammation. The translocator protein (TSPO) proven a reliable biomarker for positron emission tomography (PET) imaging. However, if TSPO imaging acute conditions such stroke provides strong signals, diseases more challenging. Here, we report results comparing recently developed tracers [18F]GE-180 [18F]DPA-714 with (R)-[11C]PK11195 rodent model of subtle focal inflammation. Adult male Wistar rats were stereotactically injected 1 μg lipopolysaccharide right striatum. Three days later, animals underwent 60-min PET scan (n = 6) or 6). Ten scanned either 5) only. Kinetic analysis data was performed using simplified reference tissue (SRTM) contralateral region novel data-driven input estimate binding BPND. Autoradiography immunohistochemistry confirm vivo results. At 40–60 min post-injection, dual-scanned showed significantly increased core/contralateral uptake ratio vs. same (3.41 ± 1.09 2.43 0.39, p 0.03); [18]DPA-714 did not (2.80 0.69 2.26 0.41). modelling identified higher (BPND) core LPS injection site but (R)-[11C]PK11195. A cerebellar SRTM unable distinguish differences tracer Second-generation TSPO-PET are accurately detect mild-level NI. In this model, shows BPND when compared (R)-[11C]PK11195, while not.