New PET radiotracer offers clearer view of brain inflammation

A newly developed PET radiotracer has shown the ability to produce high-quality images of real-time brain inflammation, according to research presented at the Society of Nuclear Medicine and Molecular Imaging 2025 Annual Meeting. By identifying activated immune cells in the brain, the tracer may pave the way for earlier diagnosis and more personalized treatment of a range of neurological diseases including Alzheimer's, Parkinson's, ALS, and multiple sclerosis.

Neuroinflammation-an immune response triggered by infection, toxin buildup, or injury in the central nervous system-is a key driver in the progression of many neurodegenerative and psychiatric disorders. Imaging neuroinflammation plays a critical role in diagnosis, monitoring, and treatment.

Current clinical PET imaging for neuroinflammation primarily uses tracers that target TSPO, a downstream marker that is broadly expressed across multiple cell types. Our study presents ¹⁸F-PDE-1905, a novel PET tracer specifically developed to target phosphodiesterase 4B (PDE4B)-a crucial intracellular enzyme that regulates inflammatory signaling within microglia, the immune cells of the central nervous system."

Jiahui Chen, PhD, associate scientist in the Department of Radiology and Imaging Sciences at Emory University School of Medicine in Atlanta, Georgia

Researchers began by analyzing a genomics database to assess PDE4B expression in neuroinflammatory diseases using bioinformatics tools. They then developed a mouse model of neuroinflammation and performed dynamic PET imaging using the ¹⁸F-PDE-1905 alongside the TSPO-specific tracer ¹⁸F-D2-LW223. Follow-up analyses were conducted to evaluate protein expression and confirm its correlation with the PET imaging findings.

Bioinformatics analysis revealed elevated PDE4B levels in both Parkinson's disease and multiple sclerosis patients, as well as in corresponding mouse models. PET imaging showed significantly higher uptake of ¹⁸F-PDE-1905 in the brains of diseased mice compared to controls, indicating increased tracer activity in neuroinflammatory conditions. When compared to the TSPO-specific tracer ¹⁸F-D2-LW223, ¹⁸F-PDE-1905 demonstrated superior image quality and greater brain distribution, underscoring its promise for imaging neuroinflammation.

"By directly targeting PDE4B, ¹⁸F-PDE-1905 provides a more specific and upstream view of microglial activation-an early and critical factor in the progression of many neurological diseases," said Chen. "For patients, this could mean earlier and more accurate diagnoses, better tracking of treatment effectiveness, and more personalized therapies based on direct measures of neuroinflammation. Ultimately, ¹⁸F-PDE-1905 has the potential to drive a major shift toward precision-guided care in neurodegenerative disorders."