Preclinical Evaluation of TSPO and MAO-B PET Radiotracers in an LPS Model of Neuroinflammation

Abstract

Discovery of novel PET radiotracers targeting neuroinflammation (microglia and astrocytes) is actively pursued. Employing a lipopolysaccharide (LPS) rat model, this longitudinal study evaluated the translocator protein 18-kDa radiotracer [¹⁸F]FEPPA (primarily microglia) and monoamine oxidase B radiotracers [¹¹C]L-deprenyl and [¹¹C]SL25.1188 (astrocytes preferred). Increased [¹⁸F]FEPPA binding peaked at 1 week in LPS-injected striatum whereas increased lazabemide-sensitive [¹¹C]L-deprenyl binding developed later. No increase in radiotracer uptake was observed for [¹¹C]SL25.1188. The unilateral intrastriatal LPS rat model may serve as a useful tool for benchmarking PET tracers targeted toward distinct phases of neuroinflammatory reactions involving both microglia and astrocytes.

Keywords: LPS rat model; MAO-B; Neuroinflammation; PET biomarkers; TSPO.