Evaluation of the novel TSPO radiotracer 2-(7-butyl-2-(4-(2-([18F]fluoroethoxy)phenyl)-5-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide in a preclinical model of neuroinflammation

Abstract

Translocator Protein (18 kDa, TSPO) is regarded as a useful biomarker for neuroinflammation imaging. TSPO PET imaging could be used to understand the role of neuroinflammation in brain diseases and as a tool for evaluating novel therapeutic effects. As a promising TSPO probe, [¹⁸F]DPA-714 is highly specific and offers reliable quantification of TSPO in vivo. In this study, we further radiosynthesized and evaluated another novel TSPO probe, 2-(7-butyl-2-(4-(2-[¹⁸F]fluoroethoxy)phenyl)-5-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N,N-diethylacetamide ([¹⁸F]VUIIS1018A), which features a 700-fold higher binding affinity for TSPO than that of [¹⁸F]DPA-714. We evaluated the performance of [¹⁸F]VUIIS1018A using dynamic in vivo PET imaging, radiometabolite analysis, in vitro autoradiography assays, biodistribution analysis, and blocking assays. In vivo study using this probe demonstrated high signal-to-noise ratio, binding potential (BP_ND), and binding specificity in preclinical neuroinflammation studies. Taken together, these findings indicate that [¹⁸F]VUIIS1018A may serve as a novel TSPO PET probe for neuroinflammation imaging.

Keywords: Neuroinflammation; Positron Emission Tomography (PET); TSPO; [(18)F]DPA-714; [(18)F]VUIIS1018A.