Synthesis and Preclinical Evaluation of 18F-CB86, a Novel Imidazole[1,2-a] Pyridine-Based TSPO Tracer

Abstract

Background: The translocator protein (TSPO), an 18 kDa protein localized to the outer mitochondrial membrane, is a recognized biomarker of neuroinflammation. However, its clinical translation has been limited by factors such as poor specificity, low signal-to-noise ratio, and the influence of genetic polymorphisms (rs6971). This study developed a novel TSPO tracer aimed at addressing this technical bottleneck. Methods: In this study, a novel TSPO-targeted probe, 18F-CB86, was synthesized and labeled using an automated multifunctional module. The radiochemical purity, in vitro stability, and lipid–water partition coefficient of 18F-CB86 were systematically evaluated; its biodistribution and Micro-PET/CT imaging characteristics were assessed in a rat model. Results: The automated labeling process yielded 18F-CB86 with radiochemical purity exceeding 95% and good in vitro stability. Biodistribution studies demonstrated high brain uptake and primary renal clearance. Micro-PET/CT imaging revealed a brain uptake of (SUVmax: 5.91 ± 0.81) % ID/mL at 60 min post-administration, indicating favorable imaging performance. Conclusions: These preliminary findings suggest that 18F-CB86 is a promising and specific probe for neuroinflammatory imaging and merits further clinical investigation.