Design of a deuterated TSPO tracer and its application in glioma and atherosclerotic imaging

Abstract

[¹⁸F]BIBD-239-d2 was designed by applying deuterated [¹⁸F]BIBD-239 to improve its stability. In vitro assays demonstrated that [¹⁸F]BIBD-239-d2 binds to TSPO with a high affinity (IC₅₀ = 3.5 nM). In vivo experiments showed that [¹⁸F]BIBD-239-d2 crosses the blood–brain barrier and is metabolized similarly to [¹⁸F]BIBD-239, with slight defluorination. Imaging studies in U87MG glioma models and autoradiography of MCAO brain slices confirmed that [¹⁸F]BIBD-239-d2 targeted TSPO with high specificity, providing high-contrast images of tumor areas and infarctions. In atherosclerotic micro PET imaging, [¹⁸F]BIBD-239-d2 uptake increases with an increase in plaque severity, while [¹⁸F]FDG does not show any correlation, indicating that it has an important application in the diagnosis of atherosclerosis.